Systems, devices, and methods including infection-fighting and monitoring shunts

ABSTRACT

Systems, devices, methods, and compositions are described for providing an actively controllable shunt configured to, for example, monitor, treat, or prevent an infection.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to and claims the benefit of theearliest available effective filing dates from the following listedapplications (the “Related Applications”) (e.g., claims earliestavailable priority dates for other than provisional patent applicationsor claims benefits under 35 U.S.C. §116(e) for provisional patentapplications, for any and all parent, grandparent, great-grandparent,etc. applications of the Related Applications). All subject matter ofthe Related Applications and of any and all parent, grandparent,great-grandparent, etc. applications of the Related Applications isincorporated herein by reference to the extent such subject matter isnot inconsistent herewith.

RELATED APPLICATIONS

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 11/894,031,titled SELF-STERILIZING DEVICE, naming Ralph G. Dacey, Jr.; Roderick A.Hyde; Muriel Y. Ishikawa; Eric C. Leuthardt; Nathan P. Myhrvold; DennisJ. Rivet; Michael A. Smith; Clarence T. Tegreene; Lowell L. Wood, Jr.;and Victoria Y. H. Wood as inventors, filed 17 Aug. 2007, which iscurrently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 11/973,010,titled VASCULATURE AND LYMPHATIC SYSTEM IMAGING AND ABLATION, namingRoderick A. Hyde; Edward K. Y. Jung; Nathan P. Myhrvold; Clarence T.Tegreene; Willard H. Wattenburg; Lowell L. Wood, Jr.; and Richard N.Zare as inventors, filed 3 Oct. 2007, which is currently co-pending, oris an application of which a currently co-pending application isentitled to the benefit of the filing date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 12/315,880,titled SYSTEM, DEVICES, AND METHODS INCLUDING ACTIVELY CONTROLLABLESUPEROXIDIZED WATER GENERATING SYSTEMS, naming Edward S. Boyden; RalphG. Dacey, Jr.; Gregory J. Della Rocca; Joshua L. Dowling; Roderick A.Hyde; Muriel Y. Ishikawa; Jordin T. Kare; Eric C. Leuthardt; Nathan P.Myhrvold; Dennis J. Rivet; Paul Santiago; Michael A. Smith; Todd J.Stewart; Elizabeth A. Sweeney; Clarence T. Tegreene; Lowell L. Wood,Jr.; and Victoria Y. H. Wood as inventors, filed 4 Dec. 2008, which iscurrently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 12/315,881,titled SYSTEM, DEVICES, AND METHODS INCLUDING STERILIZING EXCITATIONDELIVERY IMPLANTS WITH CRYPTOGRAPHIC LOGIC COMPONENTS, naming Edward S.Boyden; Ralph G. Dacey, Jr.; Gregory J. Della Rocca; Joshua L. Dowling;Roderick A. Hyde; Muriel Y. Ishikawa; Jordin T. Kare; Eric C. Leuthardt;Nathan P. Myhrvold; Dennis J. Rivet; Paul Santiago; Michael A. Smith;Todd J. Stewart; Elizabeth A. Sweeney; Clarence T. Tegreene; Lowell L.Wood, Jr.; and Victoria Y. H. Wood as inventors, filed 4 Dec. 2008,which is currently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 12/315,882,titled SYSTEM, DEVICES, AND METHODS INCLUDING STERILIZING EXCITATIONDELIVERY IMPLANTS WITH GENERAL CONTROLLERS AND ONBOARD POWER, namingEdward S. Boyden; Ralph G. Dacey, Jr.; Gregory J. Della Rocca; Joshua L.Dowling; Roderick A. Hyde; Muriel Y. Ishikawa; Jordin T. Kare; Eric C.Leuthardt; Nathan P. Myhrvold; Dennis J. Rivet; Paul Santiago; MichaelA. Smith; Todd J. Stewart; Elizabeth A. Sweeney; Clarence T. Tegreene;Lowell L. Wood, Jr.; and Victoria Y. H. Wood as inventors, filed 4 Dec.2008, which is currently co-pending, or is an application of which acurrently co-pending application is entitled to the benefit of thefiling date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 12/315,883,titled SYSTEM, DEVICES, AND METHODS INCLUDING ACTIVELY CONTROLLABLEELECTROMAGNETIC ENERGY-EMITTING DELIVERY SYSTEMS AND ENERGY-ACTIVATABLEDISINFECTING AGENTS, naming Edward S. Boyden; Ralph G. Dacey, Jr.;Gregory J. Della Rocca; Joshua L. Dowling; Roderick A. Hyde; Muriel Y.Ishikawa; Jordin T. Kare; Eric C. Leuthardt; Nathan P. Myhrvold; DennisJ. Rivet; Paul Santiago; Michael A. Smith; Todd J. Stewart; Elizabeth A.Sweeney; Clarence T. Tegreene; Lowell L. Wood, Jr.; and Victoria Y. H.Wood as inventors, filed 4 Dec. 2008, which is currently co-pending, oris an application of which a currently co-pending application isentitled to the benefit of the filing date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 12/315,884,titled SYSTEM, DEVICES, AND METHODS INCLUDING ACTIVELY CONTROLLABLESTERILIZING EXCITATION DELIVERY IMPLANTS, naming Edward S. Boyden, RalphG. Dacey, Jr., Gregory J. Della Rocca, Joshua L. Dowling, Roderick A.Hyde, Muriel Y. Ishikawa, Jordin T. Kare, Eric C. Leuthardt, Nathan P.Myhrvold, Dennis J. Rivet, Paul Santiago, Michael A. Smith, Todd J.Stewart, Elizabeth A. Sweeney, Clarence T. Tegreene, Lowell L. Wood,Jr., Victoria Y. H. Wood as inventors, filed 4 Dec. 2008, which iscurrently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 12/315,885,titled CONTROLLABLE ELECTROSTATIC AND ELECTROMAGNETIC STERILIZINGEXCITATION DELIVERY SYSTEMS, DEVICE, AND METHODS, naming Edward S.Boyden; Ralph G. Dacey, Jr.; Gregory J. Della Rocca; Joshua L. Dowling;Roderick A. Hyde; Muriel Y. Ishikawa; Jordin T. Kare; Eric C. Leuthardt;Nathan P. Myhrvold; Dennis J. Rivet; Paul Santiago; Michael A. Smith;Todd J. Stewart; Elizabeth A. Sweeney; Clarence T. Tegreene; Lowell L.Wood, Jr.; and Victoria Y. H. Wood as inventors, filed 4 Dec. 2008,which is currently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

For purposes of the United States Patent and Trademark Office (USPTO)extra-statutory requirements, the present application constitutes acontinuation-in-part of U.S. patent application Ser. No. 12/380,553,titled SYSTEM, DEVICES, AND METHODS INCLUDING ACTIVELY CONTROLLABLESTERILIZING EXCITATION DELIVERY IMPLANTS, naming Edward S. Boyden; RalphG. Dacey, Jr.; Gregory J. Della Rocca; Joshua L. Dowling; Roderick A.Hyde; Muriel Y. Ishikawa; Jordin T. Kare; Eric C. Leuthardt; Nathan P.Myhrvold; Dennis J. Rivet; Paul Santiago; Michael A. Smith; Todd J.Stewart; Elizabeth A. Sweeney; Clarence T. Tegreene; Lowell L. Wood; andJr.; and Victoria Y. H. Wood as inventors, filed 27 Feb. 2009, which iscurrently co-pending, or is an application of which a currentlyco-pending application is entitled to the benefit of the filing date.

The USPTO has published a notice to the effect that the USPTO's computerprograms require that patent applicants reference both a serial numberand indicate whether an application is a continuation orcontinuation-in-part. Stephen G. Kunin, Benefit of Prior-FiledApplication, USPTO Official Gazette Mar. 18, 2003, available athttp://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm. Thepresent Applicant Entity (hereinafter “Applicant”) has provided above aspecific reference to the application(s) from which priority is beingclaimed as recited by statute. Applicant understands that the statute isunambiguous in its specific reference language and does not requireeither a serial number or any characterization, such as “continuation”or “continuation-in-part,” for claiming priority to U.S. patentapplications. Notwithstanding the foregoing, Applicant understands thatthe USPTO's computer programs have certain data entry requirements, andhence Applicant is designating the present application as acontinuation-in-part of its parent applications as set forth above, butexpressly points out that such designations are not to be construed inany way as any type of commentary and/or admission as to whether or notthe present application contains any new matter in addition to thematter of its parent application(s).

All subject matter of the Related Applications and of any and allparent, grandparent, great-grandparent, etc. applications of the RelatedApplications is incorporated herein by reference to the extent suchsubject matter is not inconsistent herewith.

SUMMARY

In an aspect, the present disclosure is directed to, among other things,an implantable shunt system. The implantable shunt system includes, butis not limited to, one or more fluid-flow passageways configured toreceive a cerebrospinal fluid (CSF) of a biological subject and one ormore energy emitters. In an embodiment, the one or more energy emittersare configured to deliver at least one of an electromagnetic energystimulus, an electrical energy stimulus, an ultrasonic energy stimulus,and a thermal energy stimulus. In an embodiment, the one or more energyemitters are configured to emit an energy stimulus of a character andfor a time sufficient to inactivate an infectious agent within acerebrospinal fluid received within at least one of the one or morefluid-flow passageways. In an embodiment, the one or more energyemitters are configured to emit at least one of an electromagneticenergy stimulus, an electrical energy stimulus, an ultrasonic energystimulus, and a thermal energy stimulus of a character and for a timesufficient to induce programmed cell death (PCD) (e.g., apoptosis, deathof a cell mediated by an intracellular program, or the like) withoutsubstantially inducing necrosis of at least a portion of cells within acerebrospinal fluid received within at least one of the one or morefluid-flow passageways.

The implantable shunt system can include, but is not limited to, asurface region that is energetically actuatable between an opticallytransparent state and an optically reflective state. In an embodiment, abody structure defining at least one of the one or more fluid-flowpassageways includes one or more regions that are actively controllablebetween a transmissive state and a reflective state. In an embodiment, abody structure defining at least one of the one or more fluid-flowpassageways includes one or more regions that are actively controllablebetween a transmissive state and a less transmissive state. Theimplantable shunt system can include, but is not limited to, one or moreactively controllable reflective or transmissive components configuredto outwardly transmit or internally reflect an energy stimuluspropagated through at least one of the one or more fluid-flowpassageways. In an embodiment, at least one of the one or morefluid-flow passageways includes one or more regions that arecontrollably actuatable between an optically transparent state and anoptically reflective state.

The implantable shunt system can include, but is not limited to, asensor component configured to detect at least one of a characteristicof a cerebrospinal fluid received within one or more fluid-flowpassageways, a characteristic of a tissue proximate the one or morefluid-flow passageways, and a physiological characteristic of thebiological subject. The implantable shunt system can include, but is notlimited to, a controller configured to cause an outward-transmission orinternal-reflection of an energy stimulus propagated through at leastone of the one or more fluid-flow passageways based on detectedinformation from the sensor component.

The implantable shunt system can include, but is not limited to, one ormore optical materials forming at least a portion of a body structuredefining the one or more fluid-flow passageways. In an embodiment, oneor more of the optical materials are configured to limit an amount of anenergy stimulus that can traverse within the one or more fluid-flowpassageways and through an outer surface of the body structure. Theimplantable shunt system can include, but is not limited to, one or moreoptical materials on at least a portion of a body structure defining theone or more fluid-flow passageways. In an embodiment, one or more of theoptical materials are present in a sufficient amount to internallyreflect at least a portion of an emitted energy stimulus from the one ormore energy emitters into an interior of at least one of the one or morefluid-flow passageways. The implantable shunt system can include, but isnot limited to, at least one of an outer internally reflective coatingand an inner internally reflective coating on a body structure definingthe one or more fluid-flow passageways.

In an embodiment, a body structure defining at least one of the one ormore fluid-flow passageways includes one or more surface regions thatare energetically actuatable between a substantially hydrophobic stateand a substantially hydrophilic state. In an embodiment, a bodystructure defining at least one of the one or more fluid-flowpassageways includes one or more surface regions energeticallyactuatable between at least a first hydrophilic state and a secondhydrophilic state. In an embodiment, a body structure defining at leastone of the one or more fluid-flow passageways includes one or moresurface regions energetically actuatable between a hydrophobic state anda hydrophilic state. In an embodiment, a body structure defining atleast one of the one or more fluid-flow passageways includes one or moresurface regions having a material that is switchable between azwitterionic state and a non-zwitterionic state. In an embodiment, oneof the one or more fluid-flow passageways includes one or more surfaceregions energetically actuatable between an antimicrobial state and anon-fouling state.

The implantable shunt system can include, but is not limited to, one ormore sensors configured to detect at least one characteristic associatedwith the cerebrospinal fluid of the biological subject. The implantableshunt system can include, but is not limited to, a means for detectingat least one characteristic associated with the cerebrospinal fluid ofthe biological subject. The implantable shunt system can include, but isnot limited to, one or more processors configured to perform acomparison of the at least one characteristic associated with thecerebrospinal fluid to stored reference data, and to generate a responsebased at least in part on the comparison.

The implantable shunt system can include, but is not limited to, one ormore sensors configured to detect at least one characteristic associatedwith a tissue proximate the one or more fluid-flow passageways. Theimplantable shunt system can include, but is not limited to, an activeagent assembly including at least one disinfecting agent reservoir. Inan embodiment, the active agent assembly is configured to deliver one ormore disinfecting agents from the at least one disinfecting agentreservoir to an interior of at least one of the one or more fluid-flowpassageways.

The implantable shunt system can include, but is not limited to,circuitry configured to obtain information and circuitry configured forproviding information. In an embodiment, the circuitry configured toobtain information includes circuitry configured to obtain informationassociated with a delivery of the energy stimulus. In an embodiment, thecircuitry configured to obtain information includes circuitry configuredto obtain at least one of a command stream, a software stream, and adata stream. The implantable shunt system can include, but is notlimited to, at least one of a receiver configured to acquire informationbased at least in part on a sensed characteristic associated with acerebrospinal fluid received within at least one of the one or morefluid-flow passageways; a receiver configured to acquire informationbased at least in part on a detected characteristic associated with atissue proximate the one or more fluid-flow passageways; a receiverconfigured to acquire information based at least in part on a detectedphysiological characteristic associated with the biological subject; atransmitter configured to send information based at least in part on adetected characteristic associated with a cerebrospinal fluid receivedwithin at least one of the one or more fluid-flow passageways; and atransmitter configured to send a request for transmission of at leastone of data, a command, an authorization, an update, and a code.

The implantable shunt system can include, but is not limited to, one ormore computer-readable memory media having cerebrospinal fluidinformation configured as a data structure. In an embodiment, the datastructure includes at least one of psychosis state marker information,psychosis trait marker information, and psychosis indicationinformation. In an embodiment, the data structure includes at least oneof psychosis state indication information, psychosis trait indicationinformation, and predisposition for a psychosis indication information.In an embodiment, the data structure includes at least one of infectionindication information, inflammation indication information, diseasedstate indication information (e.g., an absence, a presence, or aseverity indication information), and diseased tissue indicationinformation.

The implantable shunt system can include, but is not limited to, anactively controllable excitation component configured to deliver anenergy stimulus, in vivo, to a tissue proximate a portion of the one ormore fluid-flow passageways. In an embodiment, the actively controllableexcitation component is configured to deliver a sterilizing stimulus, invivo, to a tissue proximate a portion of the one or more fluid-flowpassageways.

In an aspect, the present disclosure is directed to, among other things,an indwelling shunt apparatus including a body structure having an outersurface and an inner surface defining one or more fluid-flow passagewaysconfigured to receive a cerebrospinal fluid of a biological subject. Thebody structure of the indwelling shunt apparatus can include, amongother things, a plurality of actuatable regions that are independentlyactuatable between at least a first transmissive state and a secondtransmissive state. In an embodiment, the indwelling shunt apparatusincludes a sensor component including one or more sensors configured todetect at least one characteristic associated with a biological sampleproximate at least one of the outer surface and the inner surface of thebody structure. In an embodiment, the indwelling shunt apparatusincludes one or more energy emitters configured to emit an energystimulus based at least in part on at least one detected characteristicassociated with the biological sample.

In an aspect, the present disclosure is directed to, among other things,an implantable fluid management device. The implantable fluid managementdevice can include, but is not limited to, a shunt assembly defining oneor more fluid-flow passageways configured to receive a biological fluid(e.g., bodily fluid, blood, amniotic fluid, ascites, bile, cerebrospinalfluid, interstitial fluid, pleural fluid, transcellular fluid, or thelike) of a subject. The implantable fluid management device can include,but is not limited to, a first actively-controllable excitationcomponent configured to deliver, in vivo, a first sterilizing energystimulus to a biological fluid received within at least one of the oneor more fluid-flow passageways. The implantable fluid management devicecan include, but is not limited to, a second actively controllableexcitation component configured to deliver, in vivo, a secondsterilizing energy stimulus to a tissue proximate an outer surface ofthe implantable fluid management device. In an embodiment, theimplantable fluid management device is configured to concurrently orsequentially deliver a first sterilizing stimulus to a biological fluidreceived within at least one of the one or more fluid-flow passagewaysand a second sterilizing energy stimulus to a tissue proximate an outersurface of the implantable fluid management device. In an embodiment,the first sterilizing stimulus includes at least one of a delivery of asterilizing energy stimulus and a delivery of a sterilizing agent, andthe second sterilizing stimulus includes the other of the delivery ofthe sterilizing energy stimulus or the delivery of the sterilizingagent. In an embodiment, the first sterilizing stimulus includes atleast one of an electromagnetic sterilizing stimulus, an electricalsterilizing stimulus, an ultrasonic sterilizing stimulus, and a thermalsterilizing stimulus, and the second sterilizing stimulus includes adifferent one of an electromagnetic sterilizing stimulus, an electricalsterilizing stimulus, an ultrasonic sterilizing stimulus, or a thermalsterilizing stimulus. In an embodiment, the implantable fluid managementdevice is configured to concurrently or sequentially deliver the firststerilizing energy stimulus to a biological fluid received within atleast one of the one or more fluid-flow passageways and the secondsterilizing energy stimulus to a tissue proximate an outer surface ofthe implantable fluid management device. The implantable fluidmanagement device can include, but is not limited to, a control meansoperably coupled to at least one of the first actively controllableexcitation component and the second actively controllable excitationcomponent.

In an aspect, the present disclosure is directed to, among other things,an implantable fluid management device including a shunt assemblydefining one or more fluid-flow passageways configured to receive abiological fluid of a subject. The implantable fluid management devicecan include, but is not limited to, one or more of shunts (e.g.,blalock-taussig shunts, cardiac shunts, cerebral shunts (e.g.,cerebrospinal fluid shunts, ventriculo-atrial shunts,ventriculo-peritoneal shunts, or the like) glaucoma shunts, mechanicalshunts, pulmonary shunts, portosystemic shunts, portoacaval shunts,ventricle-to-pulmonary artery conduits, or the like), reservoirs (e.g.,active agent reservoirs, cerebrospinal fluid reservoirs, drainagereservoirs, or the like), valve assemblies (including one or moreadjustable pressure valves, mono-pressure valves, mechanical valves,electro-mechanical values, programmable valves, pulsar valves, shuntvalves, or the like), and valve mechanisms (e.g., ball-in-conemechanism).

The implantable fluid management device can include, but is not limitedto, an actively controllable excitation component configured toindependently deliver, in vivo, at least one of a first sterilizingenergy stimulus to a biological fluid received within at least one ofthe one or more fluid-flow passageways and a second sterilizing energystimulus to a tissue proximate an outer surface of the implantable fluidmanagement device. The implantable fluid management device can include,but is not limited to, a control means operably coupled to the activelycontrollable excitation component.

In an aspect, the present disclosure is directed to, among other things,an in vivo method of treating an infectious agent. The method includes,but is not limited to, providing an energy stimulus for a time andamount sufficient to inactivate an infectious agent within acerebrospinal fluid received within one or more fluid-flow passagewaysof an indwelling implant. The method includes, but is not limited to,providing an energy stimulus for a time and amount sufficient to induceprogrammed cell death of an infectious agent within a cerebrospinalfluid received within one or more fluid-flow passageways of anindwelling implant. In an embodiment, the method includes providing anenergy stimulus to an interior of an indwelling implant via one or moreenergy-emitting components that are energetically coupleable to aninterior of the one or more fluid-flow passageways. The method caninclude, but is not limited to, delivering an antimicrobial agentcomposition to a cerebrospinal fluid received within at least one ormore fluid-flow passageways.

In an aspect, the present disclosure is directed to, among other things,a method of inhibiting a microbial colonization in the cerebrospinalfluid of a biological subject. The method includes, but is not limitedto, selectively energizing one or more regions of at least onefluid-flow passageway of an indwelling cerebrospinal fluid managementsystem via one or more energy-emitting components in opticalcommunication with an interior of the least one fluid-flow passageway.In an embodiment, the method includes energizing a cerebrospinal fluidreceived within the one or more regions of the at least one fluid-flowpassageway with an energy stimulus having an operational fluence of theone or more energy emitters is less than about 80 milli-joules persquare centimeter.

In an aspect, a method includes, but is not limited to, selectivelyenergizing one or more regions of at least one fluid-flow passageway ofan in vivo implanted cerebrospinal fluid management system in responseto an automatically detected optical density parameter associated with acerebrospinal fluid received within the at least one fluid-flowpassageway.

In an aspect, a method includes, but is not limited to, providing anenergy stimulus to an interior of one or more fluid-flow passageways ofan in vivo implanted cerebrospinal fluid management device in responseto a change in a refractive index parameter associated with acerebrospinal fluid received within the at least one fluid-flowpassageway. In an embodiment, the method includes providing a spatiallypatterned energy stimulus having at least a first region and a secondregion different from the first region. In an embodiment, the firstregions comprises one of a spatially patterned electromagnetic energystimulus, a spatially patterned electrical energy stimulus, a spatiallypatterned ultrasonic energy stimulus, or a spatially patterned thermalenergy stimulus, and the second region comprises a different one of aspatially patterned electromagnetic energy stimulus, a spatiallypatterned electrical energy stimulus, a spatially patterned ultrasonicenergy stimulus, or a spatially patterned thermal energy stimulus.

In an aspect, a method includes, but is not limited to, delivering oneor more energy stimuli to at least one of an interior and an exterior ofone or more fluid-flow passageways of an indwelling cerebrospinal fluidmanagement apparatus in response to an in vivo detected change in arefractive index parameter associated with a cerebrospinal fluidreceived within the one or more fluid-flow passageways. In anembodiment, the method includes directing a first portion of an emittedenergy stimulus along a substantially lateral direction in the interiorof at least one of the one or more fluid-flow passageways and directinga second portion of the emitted energy stimulus along a substantiallylongitudinal direction in the interior of at least one of the one ormore fluid-flow passageways. In an embodiment, the method includesdirecting at least a first portion of an emitted energy stimuli, via afirst optical component, along a substantially lateral direction in afirst region of at least one of the one or more fluid-flow passagewaysand directing at a second portion of the emitted energy stimulus, via asecond optical component, along a substantially lateral direction in asecond region of the one or more fluid-flow passageways, the secondregion different from the first region. In an embodiment, the methodincludes directing a portion of an emitted energy stimulus along asubstantially longitudinal direction in a first region of at least oneof the one or more fluid-flow passageways and directing a portion of theemitted energy stimulus along a substantially longitudinal direction ina second region of the one or more fluid-flow passageways, the secondregion different from the first region. In an embodiment, the methodincludes directing at least a portion of an emitted energy stimulusalong a substantially lateral direction in a first region of at leastone of the one or more fluid-flow passageways and directing at least aportion of the emitted energy stimulus along a substantially lateraldirection in a second region of the one or more fluid-flow passageways,the second region different from the first region.

In an aspect, a method includes, but is not limited to, concurrently orsequentially delivering two or more energy stimuli to an interior and anexterior of one or more fluid-flow passageways of an indwellingcerebrospinal fluid management apparatus in response to a detectedparameter. In an embodiment, the detected parameter is associated withone or more of a cerebrospinal fluid received within the one or morefluid-flow passageways, a tissue proximate an outer surface of the oneor more fluid-flow passageways, or a physiological characteristicassociated with a biological subject. In an embodiment, the methodincludes concurrently or sequentially delivering at least a first energystimulus and a second energy stimulus, the second energy stimulusdifferent from the first energy stimulus. In an embodiment, the firstenergy stimulus comprises one of an electromagnetic energy stimulus, anelectrical energy stimulus, an ultrasonic energy stimulus, or a thermalenergy stimulus, and the second energy stimulus comprises a differentone of an electromagnetic energy stimulus, an electrical energystimulus, an ultrasonic energy stimulus, or a thermal energy stimulus.In an embodiment, the second energy stimulus comprises a differentspatial pattern from the first energy stimulus. In an embodiment, thesecond energy stimulus comprises a different temporal pattern from thefirst energy stimulus.

In an aspect, a method includes, but is not limited to, comparing, viaintegrated circuitry, one or more characteristics communicated from animplanted shunt device to stored reference data. In an embodiment, theone or more characteristics include at least one of informationassociated with a cerebrospinal fluid received within one or morefluid-flow passageways of the implanted shunt device, informationassociated with a tissue proximate a surface of the implanted shuntdevice, and information associated with a physiological characteristicof the biological subject. The method can include, but is not limitedto, initiating a treatment protocol based at least in part on thecomparison.

In an aspect, the present disclosure is directed to, among other things,an implantable shunt system. The implantable shunt system includes,among other things, a body structure having a surface defining one ormore fluid-flow passageways configured to receive a biological fluid ofa biological subject, and one or more energy emitters configured to emita pulsed thermal sterilizing stimulus of a character and for a timesufficient to induce programmed cell death (PCD) (e.g., apoptosis)without substantially inducing necrosis of at least a portion of cellswithin the biological fluid proximate the surface of the body structurein response to a determination that an infectious agent is presentwithin the biological fluid. In an embodiment, the one or more energyemitters configured to emit a pulsed thermal sterilizing stimulus of acharacter and for a time sufficient to induce PCD without substantiallyinducing necrosis of at least a portion of cells proximate the bodystructure in response to the comparison. In an embodiment, at least oneof the one or more energy emitters is configured to emit a pulsedthermal sterilizing stimulus of a character and for a time sufficient toinduce PCD without substantially inducing necrosis of an infectiousagent within a tissue proximate body structure in response to a detectlevel of an infectious agent.

In an aspect, the present disclosure is directed to, among other things,a method of inhibiting a microbial colonization in the cerebrospinalfluid of a biological subject. The method includes selectivelyenergizing one or more regions of at least one cerebrospinal fluid-flowpassageway of an indwelling implant via one or more pulsed thermalstimuli emitting components in response to an automatically detectedoptical density parameter associated with a cerebrospinal fluid receivedwithin the at least one cerebrospinal fluid-flow passageway. In anembodiment, selectively energizing includes concurrently or sequentiallydelivering at least a first pulsed thermal stimulus to a first regionand a second pulsed thermal stimulus to a second region.

In an aspect, a method includes, but is not limited to, providing apulsed thermal sterilizing stimulus to an interior of at least onecerebrospinal fluid-flow passageway of an implanted device in responseto a change in a refractive index parameter indicative of a presence ofan infectious agent within the at least one cerebrospinal fluid-flowpassageway of the implanted device. In an embodiment, providing thepulsed thermal sterilizing stimulus includes providing a spatiallypatterned pulsed thermal sterilizing stimulus having at least a firstregion and a second region different from the first region. In anembodiment, providing the pulsed thermal sterilizing stimulus includesdelivering a pulsed thermal sterilizing stimulus including at least afirst pulsed waveform segment and a second pulsed waveform segment, thesecond pulsed waveform segment having a spatial profile different fromthe first pulsed waveform segment.

In an aspect, a method includes, but is not limited to, delivering oneor more pulsed thermal stimuli to at least one of an interior or anexterior of a cerebrospinal fluid-flow passageway of an indwellingimplant apparatus in response to an in vivo detected change in arefractive parameter indicative of a presence of an infectious agentproximate the exterior or the interior of the cerebrospinal fluid-flowpassageway. In an embodiment, delivering the one or more pulsed thermalstimuli includes delivering one or more pulsed thermal stimuli to atleast one of an interior or an exterior of a cerebrospinal fluid-flowpassageway of an indwelling cerebrospinal fluid management implant.

In an aspect, a method includes, but is not limited to, concurrently orsequentially delivering two or more energy stimuli to an interiorsurface and an exterior surface of a body structure of an indwellingapparatus in response to a detected parameter associated with one ormore of a cerebrospinal fluid received within the interior of the bodystructure, a detected parameter associated with a tissue proximate theexterior surface, and a physiological characteristic associated with abiological subject.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the drawings and the followingdetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A is a perspective view of a system including an implantabledevice according to one illustrated embodiment.

FIG. 1B is a top plan view of a portion of an implantable deviceincluding a flow-regulating device according to one illustratedembodiment.

FIG. 2 is a perspective view of a system including an implantable deviceaccording to one illustrated embodiment.

FIG. 3 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 4A is a top plan view of a portion of an implantable deviceincluding one or more energy emitters in the form of a patterned energyemitter, according to one illustrated embodiment.

FIG. 4B is a top plan view of a portion of an implantable deviceincluding one or more energy emitters in the form of a patterned energyemitter, according to one illustrated embodiment.

FIG. 5A is a top plan view of a portion of an implantable deviceincluding one or more energy emitters in the form of a patterned energyemitter, according to one illustrated embodiment.

FIG. 5B is a top plan view of a portion of an implantable deviceincluding one or more energy emitters in the form of a patterned energyemitter, according to one illustrated embodiment.

FIG. 6 is a top plan view of portion of an implantable device includingone or more energy emitters according to one illustrated embodiment.

FIG. 7 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 8 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 9 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 10 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 11 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 12 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 13 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 14 is a schematic diagram of a system including an implantabledevice according to one illustrated embodiment.

FIG. 15 is a flow diagram of a method according to one illustratedembodiment.

FIG. 16 is a flow diagram of a method according to one illustratedembodiment.

FIG. 17 is a flow diagram of a method according to one illustratedembodiment.

FIG. 18 is a flow diagram of a method according to one illustratedembodiment.

FIG. 19 is a flow diagram of a method according to one illustratedembodiment.

FIG. 20 is a flow diagram of a method according to one illustratedembodiment.

FIG. 21 is a flow diagram of a method according to one illustratedembodiment.

FIG. 22 is a flow diagram of a method according to one illustratedembodiment.

FIG. 23 is a flow diagram of a method according to one illustratedembodiment.

FIG. 24 is a flow diagram of a method according to one illustratedembodiment.

FIG. 25 is a flow diagram of a method according to one illustratedembodiment.

FIGS. 26A and 26B are flow diagrams of a method according to oneillustrated embodiment.

FIG. 27 is a flow diagram of a method according to one illustratedembodiment.

FIG. 28 is a flow diagram of a method according to one illustratedembodiment.

FIG. 29 is a flow diagram of a method according to one illustratedembodiment.

FIG. 30 is a flow diagram of a method according to one illustratedembodiment.

FIG. 31 is a flow diagram of a method according to one illustratedembodiment.

FIG. 32 is a flow diagram of a method according to one illustratedembodiment.

FIG. 32 is a flow diagram of a method according to one illustratedembodiment.

FIG. 34 is a flow diagram of a method according to one illustratedembodiment.

FIG. 35 is a flow diagram of a method according to one illustratedembodiment.

FIG. 36 is a flow diagram of a method according to one illustratedembodiment.

FIG. 37 is a flow diagram of a method according to one illustratedembodiment.

FIG. 38 is a flow diagram of a method according to one illustratedembodiment.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part hereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments can be utilized, and other changes can be made,without departing from the spirit or scope of the subject matterpresented here.

Implantable shunts (e.g., cardiac shunts, cerebral shunts, portacavalshunts, portosystemic shunts, pulmonary shunts, or the like), catheters(e.g., central venous catheters, multi-lumen catheters, peripherallyinserted central catheters, Quinton catheters, Swan-Ganz catheters,tunneled catheters, or the like), or medical ports (e.g., arterialports, low profile ports, multi-lumen ports, vascular ports, or thelike) are useful for, among other things, managing movement of fluids;directly detecting (e.g., assessing, calculating, evaluating,determining, gauging, identifying, measuring, monitoring, quantifying,resolving, sensing, or the like) mechanical, physical, or biochemicalinformation (e.g., the presence of a biomarker, intracranial pressure,blood pressure, a disease state, or the like) associated with abiological subject; draining or collecting body fluids; as well as foradministering therapeutics, medications, pharmaceuticals, intravenousfluids, blood products, or parenteral nutrition.

Infections, malfunctions (e.g., blocked or clogged fluid-flowpassageways), and failures account for many of the complicationsassociated with implantable devices and pose tremendous consequences forpatients. For example, during an infection, an infectious agent (e.g.,fungi, micro-organisms, parasites, pathogens (e.g., viral pathogens,bacterial pathogens, or the like), prions, viroids, viruses, or thelike) generally interferes with the normal functioning of a biologicalsubject, and causes, in some cases, chronic wounds, gangrene, loss of aninfected tissue, loss of an infected limb, and occasionally death of thebiological subject. Implant-associated infections account for asignificant amount of nosocomial infections and despite sterilizationand aseptic procedures, remain as a major impediment to medical implantsincluding artificial hearts, artificial joints, artificial prosthetics,breast implants, catheters, contact lens, implantable biological fluiddrainage system, mechanical heart valves, stents, subcutaneous sensors,shunts, vertebral spacers, and the like. Implant-associated infectionsare often difficult to detect, problematic to cure, and at timesexpensive to manage. For example, in cases where the infection does notquickly subside, it sometimes becomes necessary to remove the implant.Implant-associated infections can result from bacterial adhesion andsubsequent biofilm formation proximate an implantation site. Forexample, biofilm-forming microorganisms sometimes colonize implants.Once a biofilm-induced infection takes hold, it can prove difficult totreat.

An aspect includes systems, devices, and methods, described hereinprovide an implantable device configured to, for example, detect (e.g.,assess, calculate, evaluate, determine, gauge, identify, measure,monitor, quantify, resolve, sense, or the like) an infectious agentpresent in, for example, a biological fluid. A non-limiting exampleincludes systems, devices, and methods including an implantable deviceconfigured to, for example, detect an infectious agent present in, forexample, a tissue proximate an implantable device.

An aspect includes systems, devices, methods, and compositions foractively detecting, treating, or preventing an infection, a fluid vesselabnormality (e.g., an obstruction), a biological fluid abnormality(e.g., cerebrospinal fluid abnormality, hematological abnormality,components concentration or level abnormality, flow abnormality, or thelike), or the like. A non-limiting example includes systems, devices,and methods for actively detecting, treating, or preventing an infectionassociated with a shunt or catheter. An aspect includes systems,devices, and methods for managing movement of fluids; directly detectingand monitoring functions or conditions (e.g., mechanical, physical,physiological, or biochemical functions or conditions) associated with abiological subject; draining or collecting body fluids; providing accessto an interior of a biological subject; distending at least onepassageway; as well as for administering therapeutics, medications,pharmaceuticals, intravenous fluids, or parenteral nutrition. Anon-limiting example includes systems, devices, and methods for activelydetecting, treating, or preventing fluid-flow obstructions in shunts orcatheters.

FIGS. 1A and 1B show a system 100 (e.g., an implantable system, animplantable shunt system, an implantable catheter system, a partiallyimplantable system, or the like) in which one or more methodologies ortechnologies can be implemented such as, for example, managing atransport of biological fluids and actively detecting, treating, orpreventing an infection (e.g., an implant-associated infection, ahematogenous associated infection, an infection present in tissue orbiological fluid, or the like), a biological fluid abnormality (e.g., acerebral spinal fluid abnormality, a hematological abnormality, or thelike), or the like.

In an embodiment, the system 100 is configured to, among other things,treat a condition associated with an infection. In an embodiment, thesystem 100 is configured to, among other things, inhibit a microbialcolonization in a biological fluid (e.g., bodily fluid, blood, amnioticfluid, ascites, bile, cerebrospinal fluid, interstitial fluid, pleuralfluid, transcellular fluid, or the like) of a biological subject. In anembodiment, the system 100 is configured to, among other things, reducethe in vivo concentration of, for example, an infectious agent presentin a biological fluid managed by the system 100. In an embodiment, thesystem 100 is configured to, among other things, reduce theconcentration of, for example, an infectious agent in the immediatevicinity of an indwelling implant. In an embodiment, the system 100 isconfigured to, among other things, reduce the risk of infection. In anembodiment, the system 100 is configured to, among other things,controllably deliver one or more energy stimuli to at least one of aninterior and an exterior of one or more fluid-flow passageways of anindwelling implant. In an embodiment, the system 100 is configured toprovide antimicrobial therapy.

The system 100 can include, but is not limited to, one or moreimplantable devices 102. An implantable device 102 is configured to,among other things, have numerous configurations. In an embodiment, theimplantable device 102 is configured to manage a transport of biologicalfluids and actively detect, treat, or prevent an infection, a biologicalfluid abnormality, or the like. For example, in an embodiment, theimplantable device 102 is configured to treat a pathological conditionassociated with an imbalance between the production and absorption ofcerebrospinal fluid. The system 100 can include partially or completelyimplantable devices 102 or components that are partially or completelyimplantable.

Among implantable devices 102 examples include, but are not limited to,shunts (e.g., cardiac shunts, cerebral shunts, cerebrospinal fluidshunts (an example of which is shown on FIG. 1), lumbo-peritonealshunts, portacaval shunts, portosystemic shunts, pulmonary shunts, orthe like), catheters (e.g., central venous catheters, multi-lumencatheters, peripherally inserted central catheters, Quinton catheters,Swan-Ganz catheters, tunneled catheters, urinary catheters, vascularcatheters, or the like), medical ports (e.g., arterial ports, lowprofile ports, multi-lumen ports, vascular ports, or the like), and thelike. Further non-limiting examples of implantable devices 102 includebio-implants, bioactive implants, breast implants, cochlear implants,dental implants, neural implants, orthopedic implants, ocular implants,prostheses, implantable electronic device, implantable medical devices,and the like.

Further non-limiting examples of implantable devices 102 includereplacements implants (e.g., joint replacements implants such, forexample, elbows, hip, knee, shoulder, wrists replacements implants, orthe like), subcutaneous drug delivery devices (e.g., implantable pills,drug-eluting stents, or the like), stents (e.g., coronary stents,peripheral vascular stents, prostatic stents, urethral stents, vascularstents, or the like), biological fluid flow controlling implants, andthe like. Further non-limiting examples of implantable devices 102include artificial hearts, artificial joints, artificial prosthetics,contact lens, mechanical heart valves, subcutaneous sensors, and thelike.

The implantable device 102 can include, but is not limited to, a bodystructure 104 having one or more fluid-flow passageways 106. In anembodiment, the body structure 104 includes at least one outer surface108 and at least one inner surface 110 defining one or more fluid-flowpassageways 106. The one or more fluid-flow passageways 106 can take avariety of shapes, configurations, and geometric forms including regularor irregular forms and can have a cross-section of substantially anyshape including, but not limited to, circular, triangular, square,rectangular, polygonal, regular or irregular shapes, or the like, aswell as other symmetrical and asymmetrical shapes, or combinationsthereof. In an embodiment, one or more portions of the body structure104 take a substantially cylindrical geometric form (e.g., a tubularstructure) having an inner surface 110 defining one or more fluid-flowpassageways 106. The substantially cylindrical geometric form can have across-section of substantially any shape including but not limited tocircular, triangular, square, rectangular, polygonal, regular orirregular shapes, or the like, as well as other symmetrical andasymmetrical shapes, or combinations thereof. In an embodiment, thesubstantially cylindrical geometric form includes multi-lumen structures(e.g., multi-lumen tubing) having multiple fluid-flow passageways 106running therethrough. In an embodiment, the body structure 104 includesone or more tubular structures (e.g., multilayer tubular structures,tubular catheter body structures, tubular shunt body structures,multi-lumen tubular structures, or the like) defining one or morefluid-flow passageways 106. In an embodiment, the implantable device 102includes a body structure 104 having one or more fluid-flow passageways106 configured to receive a cerebrospinal fluid of a biological subject.

In an embodiment, the body structure 104 includes a plurality ofconnected segments 104 a, 104 b, 104 c. In an embodiment, the bodystructure 104 includes a plurality of segments 104 a, 104 b, 104 ccoupled along a longitudinal length. In an embodiment, the bodystructure 104 includes a plurality of segments 104 a, 104 b, 104 c influid communication. In an embodiment, the body structure 104 includes aplurality of segment 104 a, 104 b, 104 c connected via separatecomponents. In an embodiment, the body structure 104 is configured as amonolithically structure. In an embodiment, the body structure 104comprises an integrally formed component assembly. In an embodiment, thebody structure 104 includes a plurality of segments configured in fluidcommunication 104 a, 104 b, 104 c that are configured to transport abiological fluid.

In an embodiment, the implantable device 102 includes a body structure104 including one or more shunts 112. In an embodiment, the implantabledevice 102 includes one or more shunts 112 configured to manage thetransport of a body fluid (e.g., cerebrospinal fluid) from one regionwithin the body (e.g. cerebral ventricle, lumbar sub-arachnoid spaces,or the like) to another (e.g., right atrium of the heart, peritonealcavity, or the like). The implantable device 102 can include, but is notlimited to, a body structure 104 including one or more shunts 112 eachhaving a proximal portion 114, a distal portion 116, and at least oneinner fluid-flow passageway 106 extending therethrough.

Among shunts, examples include, but are not limited to, blalock-taussigshunts, cardiac shunts, cerebral shunts (e.g., cerebrospinal fluidshunts, ventriculo-atrial shunts, ventriculo-peritoneal shunts, or thelike) glaucoma shunts, mechanical shunts, pulmonary shunts,portosystemic shunts, portoacaval shunts, ventricle-to-pulmonary arteryconduits, and the like. Further non-limiting examples of shunts may befound in, for example the following documents (the contents of which areincorporated herein by reference): U.S. Patent Publication Nos.2008/0039768 (published Feb. 14, 2008) and 2006/0004317 (published Jan.5, 2006).

In an embodiment, one or more of the shunts 112 are configured toregulate a pressure or flow of fluid (e.g., cerebrospinal fluid) fromthe ventricles. For example, an implantable device 102 including one ormore shunts 112 may be useful to manage a cerebrospinal fluid transportassociated with hydrocephalus (a condition including enlargedventricles). In hydrocephalus, pressure from the cerebrospinal fluidgenerally increases. Hydrocephalus develops when cerebrospinal fluidcannot flow through the ventricular system, or when absorption into theblood stream is not the same as the amount of cerebrospinal fluidproduced. Indicators for hydrocephalus include headache, personalitydisturbances and loss of intellectual abilities (dementia), problems inwalking, irritability, vomiting, abnormal eye movements, a low level ofconsciousness, and the like. Normal pressure hydrocephalus is associatedwith progressive dementia, problems in walking, and loss of bladdercontrol (urinary incontinence).

The implantable device 102 is configured to, among other things, managea transport of biological fluids. The implantable device 102 caninclude, but is not limited to, one or more ports 118 configured toprovide access from, or to, an interior environment of at least one ofthe one or more fluid-flow passageways 106. In an embodiment, theimplantable device 102 includes one or more fluid entry ports 120 andfluid exit ports 122 in fluid communication with an interior environmentof at least one of the one or more fluid-flow passageways 106 to anexterior environment. The implantable device 102 can include, but is notlimited to, one or more fluid entry ports 120 configured to providefluidic access to an interior of at least one of the one or morefluid-flow passageways 106. The implantable device 102 can include, butis not limited to, one or more fluid exit ports 122 configured toprovide fluidic access to an exterior of at least one of the one or morefluid-flow passageways 106. In an embodiment, the implantable device 102includes one or more cannulas configured to drain a cerebrospinal fluidfrom a ventricle of a brain of the biological subject. In an embodiment,the implantable device 102 includes one or more ventriculoperitonealshunts.

In an embodiment, the implantable device 102 includes one or morecerebrospinal fluid shunts configured to drain cerebrospinal fluid froma region of a brain of the biological subject. The cerebrospinal fluidshunt can include for example, but is not limit to, entry conduits, suchas a proximal (ventricular) catheter, into cranium and lateralventricle, subcutaneous conduits, such as a distal catheter, and one ormore flow-regulating devices for regulation flow of fluid out of thebrain and into a peritoneal cavity.

In an embodiment, the implantable device 102 is configured to bypassmalfunctioning arachnoidal granulations and to drain an excess fluidfrom the cerebral ventricles into one or more internal delivery regions(e.g., peritoneal cavity, pleural cavity, right atrium, gallbladder, orthe like). For example, an implantable device 102 including one or moreshunts 112 is surgically implanted to provide a controllable fluid-flowpassageway 106 that diverts cerebrospinal fluid away from centralnervous system fluid compartments (e.g., ventricles, fluid spaces nearthe spine, or the like) to one or more internal delivery regionsincluding, for example, the peritoneal cavity (ventriculo-peritonealshunt), the pleural cavity (ventriculo-pleural shunt), the right atrium(ventriculo-atrial shunt), or the gallbladder.

In an embodiment, the implantable device 102 includes one or moreflow-regulating devices 132. Among flow-regulating devices 132 examplesinclude, but are not limited to, adjustable pressure valves,mono-pressure valves, mechanical valves, electro-mechanical valves,programmable valves, pulsar valves, catheter valves, shunt valves, flowcontrolling mechanism that can be non-invasively adjusted to comport,for example, with patient's needs, or the like. Further non-limitingexamples of flow-regulating devices 132 include differential pressurevalves, one-way valves, flow-regulating or restricting valves, fixedpressure valves, (e.g., DELTA valves by Medtronic Neurological andSpinal), adjustable pressure valves (PS MEDICAL STRATA and STRATA valvesby Medtronic Neurological and Spinal), CEREBROSPINAL FLUID-flow controlvalves (Medtronic Neurological and Spinal). In an embodiment, theimplantable device 102 includes one or more flow-regulating devices 132within at least one fluid-flow passageway 106 of a shunt 114. In anembodiment, the implantable device 102 includes one or moreflow-regulating devices 132 within at least one fluid-flow passageway106 of a catheter 122.

In an embodiment, the one or more flow-regulating devices 132 include atleast one valve assemblies having one or more of a housing, inlet andoutlet ports, fluid-flow passageways 106, adjustable pressure valves,mono-pressure valves, mechanical valves, electro-mechanical valves,programmable valves, one-way valves, two-way valves, pulsar valves,shunt valves, electro-mechanical valve actuators, valve mechanisms(e.g., ball-in-cone mechanism, controllable diaphragms, valvediaphragms, or the like), valve seats, pressure control valves, shuntvalves, flow restriction devices, flow control devices, shunts,catheters, and the like. In an embodiment, the implantable device 102includes one or more pressure (e.g., intracranial pressure) regulatingdevices 132. In an embodiment, the implantable device 102 includes apressure-regulated valve means positioned within at least one fluid-flowpassageway 106 for providing fluid flow therethrough at selected fluidpressures.

In an embodiment, the implantable device 102 is configured to regulate atransport of a material into or out of a biological subject. Forexample, in an embodiment, the implantable device 102 includes one ormore flow-regulating devices 132 configured to configured to regulate atransport of a material into or out of a biological subject. Amongflow-regulating devices 132 examples include, but are not limited to,adjustable pressure valves, mono-pressure valves, mechanical valves,electro-mechanical valves, programmable valves, pulsar valves, cathetervalves, shunt valves, flow controlling mechanism that can benon-invasively adjusted to comport, for example, with patient's needs,or the like. Further non-limiting examples of flow-regulating devices132 include differential pressure valves, one-way valves,flow-regulating or restricting valves, fixed pressure valves, (e.g.,DELTA valves by Medtronic Neurological and Spinal), adjustable pressurevalves (PS MEDICAL STRATA and STRATA valves by Medtronic Neurologicaland Spinal), CEREBROSPINAL FLUID-flow control valves (MedtronicNeurological and Spinal). In an embodiment, the implantable device 102includes one or more flow-regulating devices 132 within at least onefluid-flow passageway 106 of a shunt 114. In an embodiment, theimplantable device 102 includes one or more flow-regulating devices 132within at least one fluid-flow passageway 106 of a catheter 122.

In an embodiment, the implantable device 102 is configured to regulate atransport of a material within a biological subject. In an embodiment,the implantable device 102 is configured to regulate fluidic flow in orout of a biological subject. In an embodiment, the implantable device102 is configured to regulate fluidic flow from at least a firstlocation of the body to at least a second location of the body. In anembodiment, the implantable device 102 is configured to regulate fluidicflow of cerebrospinal fluid from a ventricle of the brain to a drainagelocation in the body.

Referring to FIG. 2, in an embodiment, the implantable device 102includes a body structure 104 including a catheter assembly 202 havingone or more catheters 204. In an embodiment, the implantable device 102includes one or more catheters 204 configured to directly detecting andmonitoring mechanical, physical, or biochemical functions associatedwith a biological subject; draining or collecting body fluids; providingaccess to an interior of a biological subject; distending at least onepassageway; as well as for administering therapeutics, medications,pharmaceuticals, intravenous fluids, or nutrition. In an embodiment, theimplantable device 102 includes one or more at least partiallyimplantable catheters 204. The implantable device 102 can include, butis not limited to, one or more ports 206 configured to provide accessfrom, or to, an interior environment of at least one of the one or morefluid-flow passageways 106.

The implantable device 102 can include, but is not limited to, a bodystructure 104 including one or more catheters 204 each having a proximalportion 208, a distal portion 210, and at least one inner fluid-flowpassageway 106 extending therethrough. Among catheters 204, examplesinclude, but are not limited to, arterial catheters, dialysis catheters,drainage catheters, indwelling catheters, long term non-tunneled centralvenous catheters, long term tunneled central venous catheters,mechanical catheters, peripheral venous catheters, peripherallyinsertable central venous catheters, peritoneal catheters, pulmonaryartery Swan-Ganz catheters, short-term central venous catheters, urinarycatheters, ventricular catheters, and the like. In an embodiment, one ormore of the catheters 204 are configured for insertion into a bodycavity, a duct, or a vessel of a subject in need thereof. In anembodiment, an implantable device 102 including a catheter assembly 202is positioned to facilitate the transport of cerebrospinal fluid from acerebral ventricle or subarachnoid space into, for example, a collectionsite, an ex vivo drainage reservoir, a partially implanted catheterassembly 202, or the like.

In an embodiment, the implantable device 102 includes one or morecatheters 204. In an embodiment, the implantable device 102 includes oneor more proximal catheters. In an embodiment, the implantable device 102includes one or more distal catheters. In an embodiment, the implantabledevice 102 includes one or more brain ventricle catheters. In anembodiment, the implantable device 102 includes one or more sinussagittalis catheters. In an embodiment, the implantable device 102includes one or more biocompatible materials, polymeric materials,thermoplastics, silicone materials (e.g., polydimethysiloxanes),polyvinyl chloride materials, laytex rubber materials, or the like.Non-limiting examples of catheters 204 or shunts 112, or componentsthereof may be found in, for example the following documents (thecontents of each of which are incorporated herein by reference): U.S.Pat. Nos. 7,524,298 (issued Apr. 28, 2009), 7,390,310 (issued Jun. 24,2008), 7,334,594 (issued Feb. 26, 2008), 7,309,330 (issued Dec. 18,2007), 7,226,441 (issued Jun. 5, 2007), 7,118,548 (issued Oct. 10,2006), 6,932,787 (issued Aug. 23, 2005), 6,913,589 (issued Jul. 5,2005), 6,743,190 (issued Jun. 1, 2004), 6,585,677 (issued Jul. 1, 2003);and U.S. Patent Publication Nos. 2009/0118661 (published May 7, 2009),2009/0054824 (published Feb. 26, 2009, 2009/0054827 (published Feb. 26,2009), 2008/0039768 (published Feb. 14, 2008), 2006/0004317 (publishedJan. 5, 2006).

FIG. 3 shows various configurations of a system 100 in which one or moremethodologies or technologies can be implemented. The system 100 caninclude, but is not limited to, one or more energy emitters 302. In anembodiment, the system 100 includes a means for emitting an energystimulus 304 including, for example, one or more energy emitters 302having one or more energy waveguides 306. In an embodiment, theimplantable device 102 includes one or more energy emitters 302. In anembodiment, the one or more energy emitters 302 are configured to emitat least one of an electromagnetic stimulus, an electrical stimulus, anultrasonic stimulus, and a thermal stimulus. In an embodiment, the oneor more energy emitters 302 are configured to generate a sterilizingenergy stimulus. In an embodiment, the one or more energy emitters 302are configured to emit at least one of an electromagnetic sterilizingstimulus, an electrical sterilizing stimulus, an ultrasonic sterilizingstimulus, and a thermal sterilizing stimulus. In an embodiment, the oneor more energy emitters 302 are configured to deliver an in vivostimulus waveform to a biological subject. In an embodiment, the one ormore energy emitters 302 are configured to generate one or morecontinuous or a pulsed energy waves, or combinations thereof. In anembodiment, the one or more energy emitters 302 are configured todeliver an emitted energy to a biological fluid or tissue proximate atleast one of an outer surface 108 and an inner surface 110 of theimplantable device 102.

In an embodiment, the one or more energy emitters 302 are configured toemit at least one of an electromagnetic stimulus, an electricalstimulus, an ultrasonic stimulus, and a thermal stimulus of a characterand for a time sufficient to inactivate an infectious agent proximate anouter or inner portion of the implantable device 102. In an embodiment,the one or more energy emitters 302 are configured to emit at least oneof an electromagnetic stimulus, an electrical stimulus, an ultrasonicstimulus, and a thermal stimulus of a character and for a timesufficient to inhibit a DNA replication process of an infectious agent.In an embodiment, the one or more energy emitters 302 are configured toemit at least one of an electromagnetic stimulus, an electricalstimulus, an ultrasonic stimulus, and a thermal stimulus of a characterand for a time sufficient to induce PCD of at least a portion of cellswithin a cerebrospinal fluid proximate the implantable device 102.

PCD can be induced using a variety of methodologies and technologiesincluding, for example, pulsed electric fields, pulsed ultrasound,focused ultrasound, low intensity ultrasound, ultraviolet radiation, orthe like. Further non-limiting examples of methodologies andtechnologies for inducing PCD can be found the following documents (thecontents of which are incorporated herein by reference): Abdollahi etal., Apoptosis signals in Lymphoblasts Induced by Focused Ultrasound,FASEB Journal Express Article doi:10.1096/fj.04-1601fje (Publishedonline Jul. 1, 2004); Ashush et al., Apoptosis Induction of HumanMyeloid Leukemic Cells by Ultrasound Exposure, Cancer Res. 60: 1014-1020(2000); Beebe et al., Nanosecond, High-intensity Pulsed Electric FieldsInduce Apoptosis in Human Cells, The FASEB Journal express article10.1096/fj.02-0859fje (Published online Jun. 17, 2003); Caricchio etal., Ultraviolet B Radiation-Induced Cell Death: Critical Role ofUltraviolet Dose in Inflammation and Lupus Autoantigen Redistribution,J. Immunol., 171: 5778-5786 (2003); Fabo et al., Ultraviolet B but notUltraviolet A Radiation Initiates Melanoma, Cancer Res. 64 (18):6372-376 (2004); Fent et al., Low Intensity Ultrasound-induced Apoptosisin Human Gastric Carcinoma Cells, World J Gastroenterol, 14(31):4873-879(2008); Hall et al., Nanosecond Pulsed Electric Fields Induce Apoptosisin p53-Wildtype and p53-Null HCT116 Colon Carcinoma Cells, Apoptosis,12(9):1721-31 (2007); and Rediske et al., Pulsed Ultrasound Enhances theKilling of Escherichia coli Biofilms by Aminoglycoside Antibiotics InVivo, Antimicrob. Agents Chemother., 44 (3): 771-72 (2000). In anembodiment, the one or more energy emitters 302 are configured to emit asufficient amount at least one of an electromagnetic stimulus, anelectrical stimulus, an ultrasonic stimulus, and a thermal stimulus toinduce PCD without substantially inducing necrosis of a portion of cellsproximate an outer or inner portion of the implantable device 102. In anembodiment, the one or more energy emitters 302 are configured todeliver electromagnetic radiation of a character and for a timesufficient to induce PCD without substantially inducing necrosis of atissue proximate the outer portion of the one or more fluid-flowpassageways 106. In an embodiment, one or more energy emitters 302 areconfigured to deliver a sufficient amount of an ultraviolet radiation toinduce cell death by PCD. In an embodiment, the one or more energyemitters 302 are configured to deliver an effective dose of opticalenergy at which a cell preferentially undergoes PCD compared tonecrosis. In an embodiment, the one or more energy emitters 302 areconfigured to deliver a sufficient amount of an optical energy toinitiate ultraviolet energy induced PCD. In an embodiment, the one ormore energy emitters 302 include at least one ultraviolet energyemitter. In an embodiment, the one or more energy emitters 302 includeat least one ultraviolet B energy emitter. In an embodiment, the one ormore energy emitters 302 include at least one ultraviolet C energyemitter. In an embodiment, at least one of the one or more energyemitters 302 comprises a peak emission wavelength ranging from about 100nanometers to about 400 nanometers. In an embodiment, at least one ofthe one or more energy emitters 302 comprises a peak emission wavelengthranging from about 100 nanometers to about 320 nanometers. In anembodiment, at least one of the one or more energy emitters 302comprises a peak emission wavelength ranging from about 280 nanometersto about 320 nanometers.

Among energy emitters 302 examples include, but are not limited to,electric circuits, electrical conductors, electrodes (e.g., nano- andmicro-electrodes, patterned-electrodes, electrode arrays (e.g.,multi-electrode arrays, micro-fabricated multi-electrode arrays,patterned-electrode arrays, or the like), electrocautery electrodes, orthe like), cavity resonators, conducting traces, ceramic patternedelectrodes, electro-mechanical components, lasers, quantum dots, laserdiodes, light-emitting diodes (e.g., organic light-emitting diodes,polymer light-emitting diodes, polymer phosphorescent light-emittingdiodes, microcavity light-emitting diodes, high-efficiency UVlight-emitting diodes, or the like), arc flashlamps, incandescentemitters, transducers, heat sources, continuous wave bulbs, ultrasoundemitting elements, ultrasonic transducers, thermal energy emittingelements, and the like. In an embodiment, the one or more energyemitters 302 include at least one two-photon excitation component. In anembodiment, the one or more energy emitters 302 include at least one ofan exciplex laser, a diode-pumped solid state laser, and a semiconductorlaser. Further non-limiting examples of energy emitters 302 includeradiation emitters, ion emitters, photon emitters, electron emitters,gamma emitters, and the like.

Energy emitters 302 forming part of the implantable device 102, can takea variety of forms, configurations, and geometrical patterns includingfor example, but not limited to, a one-, two-, or three-dimensionalarrays, a pattern comprising concentric geometrical shapes, a patterncomprising rectangles, squares, circles, triangles, polygons, anyregular or irregular shapes, or the like, or any combination thereof.One or more of the energy emitters 302 can have a peak emissionwavelength in the x-ray, ultraviolet, visible, infrared, near infrared,terahertz, microwave, or radio frequency spectrum.

In an embodiment, the one or more energy emitters 302 include one ormore optical energy emitters 308. In an embodiment, the one or moreoptical energy emitters 308 are configured to emit a sterilizing energystimulus having one or more peak emission wavelengths in the infrared,visible, or ultraviolet spectrum, or combinations thereof. In anembodiment, an operational fluence of the one or more optical energyemitters 308 is less than about 80 milli-joules per square centimeter.In an embodiment, an operational fluence of the one or more opticalenergy emitters 308 is less than about 35 milli-joules per squarecentimeter. In an embodiment, an operational fluence of the one or moreoptical energy emitters 308 is less than about 15 milli joules persquare centimeter. In an embodiment, an average energy density of theone or more optical energy emitters 308 ranges from about less thanabout 15 milli-joules per square centimeter to about less than about 80milli-joules per square centimeter.

In an embodiment, the one or more energy emitters 302 are configured togenerate one or more non-ionizing laser pulses in an amount and for atime sufficient to induce the formation of sound waves associated withchanges in a biological mass present along an optical path. In anembodiment, the one or more energy emitters 302 are configured to directa pulsed optical energy waveform along an optical path of a characterand for a time sufficient to cause a biological mass within acerebrospinal fluid interrogated by the pulsed optical energy waveformto temporarily expand. In an embodiment, the one or more energy emitters302 are configured to direct a pulsed optical energy stimulus along anoptical path in an amount and for a time sufficient to elicit theformation of acoustic waves associated with changes in a biological masspresent along the optical path. In an embodiment, the one or more energyemitters 302 are configured to direct a pulsed optical energy waveformalong an optical path of sufficient strength or duration to cause atleast a portion of cells within a cerebrospinal fluid interrogated bythe pulsed optical energy waveform to temporarily expand. In anembodiment, the one or more energy emitters 302 are configured to directa pulsed optical energy waveform along an optical path in an amount andfor a time sufficient to cause at least a portion of cells within acerebrospinal fluid interrogated by the pulsed optical energy waveformto temporarily fluoresce.

In an embodiment, the one or more energy emitters 302 are configured todirect optical energy along the optical path for a time sufficient tointeract with a cerebrospinal fluid received within one or morefluid-flow passageways 106. In an embodiment, the one or more energyemitters 302 are further configured to direct a portion of an emittedoptical energy to a sensor component in optical communication along theoptical path.

In an embodiment, the one or more energy emitters 302 are configured toconcurrently or sequentially deliver one or more electromagneticstimuli, electrical stimuli, ultrasonic stimuli, or thermal stimuli. Inan embodiment, at least one of the one or more energy emitters 302 isconfigured to deliver an electromagnetic stimulus, in vivo, to acerebrospinal fluid received within at least one of the one or morefluid-flow passageways 106. In an embodiment, at least one of the one ormore energy emitters 302 is configured to deliver an electricalstimulus, in vivo, to a cerebrospinal fluid received within at least oneof the one or more fluid-flow passageways 106. In an embodiment, atleast one of the one or more energy emitters 302 is configured todeliver an ultrasonic stimulus, in vivo, to a cerebrospinal fluidreceived within at least one of the one or more fluid-flow passageways106. In an embodiment, at least one of the one or more energy emitters302 is configured to deliver a thermal stimulus, in vivo, to acerebrospinal fluid received within at least one of the one or morefluid-flow passageways 106.

In an embodiment, at least one of the one or more energy emitters 302 isconfigured to emit at least one of an electromagnetic stimulus, anelectrical stimulus, an ultrasonic stimulus, and a thermal stimulushaving a character and for a time sufficient to induce PCD withoutsubstantially inducing necrosis of an infectious agent within acerebrospinal fluid received within at least one of the one or morefluid-flow passageways 106. In an embodiment, at least one of the one ormore energy emitters 302 is configured to emit an energy stimulus of acharacter and for a time sufficient to induce PCD without substantiallyinducing necrosis of a pathogen within a cerebrospinal fluid receivedwithin at least one of the one or more fluid-flow passageways 106. In anembodiment, at least one of the one or more energy emitters 302 isconfigured to deliver an energy stimulus of a character and for a timesufficient to induce poration (e.g., electroporation) of a plasmamembrane in at least a portion of cells within a cerebrospinal fluidreceived within at least one of the one or more fluid-flow passageways106. In an embodiment, one or more of the energy emitters 302 areconfigured to emit an energy stimulus of a character and for a timesufficient to induce PCD without substantially inducing necrosis of atleast a portion of cells within a cerebrospinal fluid received within atleast one of the one or more fluid-flow passageways 106.

In an embodiment, at least one of the one or more energy emitters 302 isphotonically coupleable to an interior of one or more of the one or morefluid-flow passageways 106. In an embodiment, at least one of the one ormore energy emitters 302 is photonically coupleable to an exterior ofone or more of the one or more fluid-flow passageways 106. In anembodiment, at least one of the one or more energy emitters 302 isphotonically coupleable, via one or more waveguides 306, to an interiorof at least one of the one or more fluid-flow passageways 106. In anembodiment, at least one of the one or more energy emitters 302 isconfigured to emit an energy stimulus from an interior of at least oneof the one or more fluid-flow passageways to an exterior of at least oneof the one or more fluid-flow passageways 106.

In an embodiment, the one or more energy emitters 302 are configured todeliver an energy stimulus to a region proximate the implantable device102. In an embodiment, the one or more energy emitters 302 areconfigured to deliver an emitted energy to tissue proximate theimplantable device 102. In an embodiment, the one or more energyemitters 302 are configured to deliver an emitted energy to tissueproximate an outer 108 or inner 110 surface of the implantable device102.

In an embodiment, the one or more energy emitters 302 are configured toemit an energy stimulus having one or more peak emission wavelengths inthe x-ray, ultraviolet, visible, infrared, near infrared, terahertz,microwave, or radio frequency spectrum. In an embodiment, least one ofthe one or more energy emitters 302 is configured to deliver one or morecharged particles. In an embodiment, the one or more energy emitters 302include one or more lasers, laser diodes, light-emitting diodes, arcflashlamps, incandescent emitters, transducers, heat sources, orcontinuous wave bulbs. In an embodiment, the one or more energy emitters302 include one or more light-emitting diodes, quantum dots, organiclight-emitting diodes, microcavity light-emitting diodes, or polymerlight-emitting diodes.

In an embodiment, the one or more energy emitters 302 are configured toprovide a voltage across at least a portion of cells within acerebrospinal fluid received within at least one of the one or morefluid-flow passageways 106. In an embodiment, the voltage is ofsufficient strength or duration to exceed a nominal dielectric strengthof at least one cell plasma membrane. In an embodiment, the voltage isof sufficient strength or duration to exceed a nominal dielectricstrength of a cell plasma membrane without substantially interferingwith a normal operation of the implantable shunt system 100.

In an embodiment, the one or more energy emitters 302 are implantedwithin a biological subject. In an embodiment, the one or more energyemitters 302 are configured to apply energy (e.g., electrical energy,electromagnetic energy, thermal energy, ultrasonic energy, or the like,or combinations thereof) to tissue proximate an implantable device 102to, for example, treat or prevent an infection (e.g., animplant-associated infection, hematogenous implant-associated infection,or the like), a hematological abnormality, or the like. In anembodiment, the one or more energy emitters 302 are configured to applyenergy to tissue proximate an implantable device 102 to promote at leastone of a tissue healing process, a tissue growing process, a tissuescarring process, and the like. In an embodiment, the one or more energyemitters 302 are configured to apply energy of sufficient strength orduration to tissue proximate an implant to inhibit a tissue scarringprocess. In an embodiment, the one or more energy emitters 302 areconfigured to apply energy to tissue proximate an implant to treat,prevent, inhibit, or reduce post-operative adhesion, fibrin sheathformation, or scar tissue formation. In an embodiment, the one or moreenergy emitters 302 are configured to apply an energy stimulus to tissueproximate an implantable device 102 to treat, prevent, inhibit, orreduce the presence or concentration of an infectious agent within atleast a portion of the tissue proximate the implantable device 102.

In an embodiment, the one or more energy emitters 302 are configured toconcurrently or sequentially deliver at least a first energy stimulusand a second energy stimulus, the second energy stimulus different fromthe first energy stimulus. In an embodiment, the second energy stimulusdiffers in at least one of a spatial distribution and a temporaldistribution. In an embodiment, the first energy stimulus comprises anelectromagnetic energy stimulus, an electrical energy stimulus, anultrasonic energy stimulus, or a thermal energy stimulus, and the secondenergy stimulus comprises a different one of an electromagnetic energystimulus, an electrical energy stimulus, an ultrasonic energy stimulus,or a thermal energy stimulus. In an embodiment, at least one of the oneor more energy emitters 302 is configured to provide an illuminationpattern comprising at least a first region and a second region. In anembodiment, the second region includes at least one of an illuminationintensity, an energy-emitting pattern, a peak emission wavelength, anON-pulse duration, an OFF-pulse duration, and a pulse frequencydifferent from the first region. In an embodiment, the second regionincludes at least one of a spatial pattern and a temporal patterndifferent from the first region.

In an embodiment, an energy emitter 302 is operably coupled to aplurality of waveguides 902 that are configured to deliver a spatiallypattern energy stimulus. In an embodiment, an energy emitter 302 isconfigures to emit a multiplex energy stimulus having two or more peakemission wavelengths. In an embodiment, a multiplex energy stimulus canbe routed to respective waveguides 902 configured to deliver a spatiallypattern energy stimulus base on a wavelength, an intensity, a spectralpower distribution, a waveguide-specific address, or the like.

The system 100 can include, but is not limited to, one or morelight-emitting diodes 310. In an embodiment, the implantable device 102includes one or more light-emitting diodes 310. Light-emitting diodes310 come in a variety of forms and types including, for example,standard, high intensity, super bright, low current types, or the like.Typically, the light-emitting diode's color is determined by the peakwavelength of the light emitted. For example, red light-emitting diodeshave a peak emission ranging from about 610 nm to about 660 nm.Non-limiting examples of light-emitting diode colors include amber,blue, red, green, white, yellow, orange-red, ultraviolet, and the like.Further non-limiting examples of light-emitting diodes include bi-color,tri-color, and the like. Light-emitting diode's emission wavelength maydepend on a variety of factors including, for example, the currentdelivered to the light-emitting diode. The color or peak emissionwavelength spectrum of the emitted light may also generally depends onthe composition or condition of the semi-conducting material used, andcan include, but is not limited to, peak emission wavelengths in theinfrared, visible, near-ultraviolet, or ultraviolet spectrum, orcombinations thereof.

Light-emitting diodes 310 can be mounted on, for example, but notlimited to a surface, a substrate, a portion, or a component of theimplantable device 102 using a variety of methodologies and technologiesincluding, for example, wire bonding, flip chip, controlled collapsechip connection, integrated circuit chip mounting arrangement, and thelike. In an embodiment, the light-emitting diodes 310 are mounted on asurface, substrate, portion, or component of the implantable device 102using, for example, but not limited to a flip-chip arrangement. Aflip-chip is one type of integrated circuit chip mounting arrangementthat generally does not require wire bonding between chips. In anembodiment, instead of wire bonding, solder beads or other elements arepositioned or deposited on chip pads such that when the chip is mounted,electrical connections are established between conductive traces carriedby circuitry within the system 100. In an embodiment, the one or moreenergy emitters 302 include one or more light-emitting diode arrays. Inan embodiment, the one or more energy emitters 302 include at least oneof a one-dimensional light-emitting diode array, a two-dimensionallight-emitting diode array, and a three-dimensional light-emitting diodearray.

The system 100 can include, but is not limited to, include one or moreultrasound energy emitters 312. In an embodiment, the implantable device102 includes one or more ultrasound energy emitters 312. In anembodiment, the one or more energy emitters 302 include one or moretransducers 314 (e.g., ultrasonic transducers, ultrasonic sensors, orthe like). In an embodiment, the one or more transducers 314 areconfigured to deliver an ultrasonic energy stimulus (e.g., an ultrasonicnon-thermal stimulus, an ultrasonic thermal stimulus, a low or highintensity ultrasonic stimulus, a pulsed ultrasonic stimulus, a focusedultrasonic stimulus, or the like) to a region within the biologicalsubject. In an embodiment, the one or more transducers 314 areconfigured to generate an ultrasonic stimulus. In an embodiment, the oneor more transducers 314 are configured to detect an ultrasonic signal.In an embodiment, the one or more transducers 314 are configured totransmit and receive ultrasonic waves. In an embodiment, the one or moretransducers 314 are configured to deliver an ultrasonic stimulus to aregion proximate the implantable device 102. In an embodiment, the oneor more transducers 314 are configured to deliver an in vivo ultrasonicinterrogation waveform to a biological subject. In an embodiment, theone or more transducers 314 are configured to generate one or morecontinuous or a pulsed ultrasonic waves, or combinations thereof.

Among transducers 314, examples include, but are not limited to,acoustic transducers, composite piezoelectric transducers, conformaltransducers, flexible transducers, flexible ultrasonic multi-elementtransducer arrays, flexible ultrasound transducers, immersibleultrasonic transducers, integrated ultrasonic transducers,micro-fabricated ultrasound transducers, piezoelectric materials (e.g.,lead-zirconate-titanate, bismuth titanate, lithium niobate,piezoelectric ceramic films or laminates, sol-gel sprayed piezoelectricceramic composite films or laminates, piezoelectric crystals, or thelike), piezoelectric ring transducers, piezoelectric transducers,ultrasonic sensors, ultrasonic transducers, and the like. In anembodiment, the one or more energy emitters 302 include one or moreone-dimensional transducer arrays, two-dimensional transducer arrays, orthree-dimensional transducer arrays. The one or more transducers 314 caninclude, but are not limited to, a single design where a singlepiezoelectric component outputs one single waveform at a time, or can becompound where two or more piezoelectric components are utilized in asingle transducer 314 or in multiple transducers 314 thereby allowingmultiple waveforms to be output sequentially or concurrently.

The effects of therapeutic ultrasound on living tissues vary. Forexample, ultrasound typically has a greater affect on highly organized,structurally rigid tissues such as bone, tendons, ligaments, cartilage,and muscle. Due to their different depths within the body, however, thedifferent tissue types require different ultrasonic frequencies foreffective treatment. See, e.g., U.S. Publication No. 2007/0249969(published Oct. 25, 2007) (the contents of which are incorporated hereinby reference). Ultrasound can cause increases in tissue relaxation,local blood flow, and scar tissue breakdown. In an embodiment, theeffect of the increase in local blood flow are used to, for example, aidin reducing local swelling and chronic inflammation, as well as promotebone fracture healing. In an embodiment, applying a sufficientultrasonic energy to tissue infected with, for example, pathogenicbacteria, can lead to a reduction of the pathogenic bacteria in at leasta portion of the infected tissue. In an embodiment, applying asufficient ultrasonic energy to tissue infected with, for example,pathogenic bacteria, in the presence of one or more disinfecting agentscan lead to a reduction of the pathogenic bacteria in at least a portionof the infected tissue. In an embodiment, applying a sufficientultrasonic energy to tissue infected with, for example, pathogenicbacteria, in the presence of one or more disinfecting agents can reducebiofilm viability, as well as actively-impeding biofilm formation on animplant.

In an embodiment, the system 100 includes electro-mechanical componentsfor generating, transmitting, or receiving waves (e.g., ultrasonicwaves, electromagnetic waves, or the like). For example, in anembodiment, the system 100 includes one or more waveform generators 316,as well as any associated hardware, software, and the like. In anembodiment, the system 100 includes one or more controllers configuredto concurrently or sequentially operate multiple transducers 314. In anembodiment, the system 100 includes multiple drive circuits (e.g., onedrive circuit for each transducer 314) and is configured to generatevarying waveforms from each coupled transducer 314 (e.g., multiplewaveform generators, or the like). The system 100 can include, but isnot limited to, an electronic timing controller coupled to an ultrasonicwaveform generator. In an embodiment, one or more controllers areconfigured to automatically control one or more of a frequency, aduration, a pulse rate, a duty cycle, an amount of energy, or the likeassociated with the ultrasonic energy generated by the one or moretransducers 314.

In an embodiment, the one or more transducers 314 are communicativelycoupled to one or more waveform generators 316. In an embodiment, awaveform generator 316 can include, but is not limited to, an oscillator318 and a pulse generator 320 configured to generate one or more drivesignals for causing one or more transducer 314 to ultrasonically vibrateand generate ultrasonic energy.

The system 100 can include, but is not limited to, one or more thermalenergy emitters 322. In an embodiment, the implantable device 102includes one or more thermal energy emitters 322. In an embodiment, theone or more thermal energy emitters 322 include one or more transducers314. In an embodiment, the one or more thermal energy emitters 322include one or more metallic heat-radiating elements. In an embodiment,the one or more thermal energy emitters 322 include one or more powerlight-emitting diodes 324. In an embodiment, the one or more thermalenergy emitters 322 include one or more thermal energy emittingelements. In an embodiment, the one or more thermal energy emitters 322include one or more thermal energy conducting elements. In anembodiment, the one or more thermal energy emitters 322 include one ormore thermal energy dissipating elements. In an embodiment, the one ormore thermal energy emitters 322 include one or more electrodes 326. Inan embodiment, the one or more thermal energy emitters 322 areconfigured to emit a sufficient amount of an energy stimulus toinactivate an infectious agent. In an embodiment, the one or morethermal energy emitters 322 are configured to thermally shock aninfectious agent. In an embodiment, the one or more thermal energyemitters 322 are configured to emit a thermal energy stimulus of acharacter and for a duration to thermally induce PCD of a portion ofinfected cells proximate the implantable device 102. In an embodiment,the one or more thermal energy emitters 322 are operable to emit asufficient amount of an energy stimulus to increase the temperature ofat least a portion of a cerebrospinal fluid received within at least oneof the one or more fluid-flow passageways 106 by about 5° C. to about20° C. In an embodiment, the one or more thermal energy emitters 322 areoperable to emit a sufficient amount of an energy stimulus to increasethe temperature of at least a portion of a cerebrospinal fluid receivedwithin at least one of the one or more fluid-flow passageways 106 byabout 5° C. to about 6° C.

The system 100 can include, but is not limited to, one or more energyemitters 302 configured to deliver a pulsed thermal sterilizing stimulusof a character and for a duration sufficient to elevate a temperature ofat least a portion of cells proximate an indwelling medical implant.Elevated temperatures or hyperthermia therapy caused by the one or moreenergy emitters 302 in a region including cells and or tissue can inducedeath of the cells and or tissue through, for example, a process ofprogrammed cell death (e.g., apoptosis) or necrosis, depending upon thetemperature experienced by the cells and or tissue. For example,hyperthermia therapy between 40° C. and 60° C. can result in disorderedcellular metabolism and membrane function and in many instances, celldeath. In general, at temperatures below 60° C., hyperthermia is morelikely to induce PCD in cells without substantially inducing necrosis.At temperatures greater than about 60° C., the likelihood of inducingcoagulation necrosis of cells and tissue increases. Relatively smallincreases in temperature, e.g., 3° C., above the normal functioningtemperature of a cell can cause apoptotic cell death. For example,temperatures ranging from 40° C. to 47° C. can induce cell death in areproducible time and temperature dependent manner in cells normallyfunctioning at 37° C.

Elevating the temperature of a mammalian cell, for example, to 43° C.can cause changes in cellular protein expression and increased PCD. Insome instances, hyperthermia can be induced by exposure to highintensity focused ultrasound (HIFU). High acoustic intensitiesassociated with HIFU can cause rapid heat generation in cells and tissuedue to absorption of the acoustic energy. Using HIFU, the temperature ina region including cells and or tissue can rise very rapidly, inducingthermal stressing of the targeted cells and or tissue which in turn canlead to apoptotic cell death. The degree of thermal stressing of cellsmay be a function of the character or duration of the energy stimulusdelivered to induce a temperature change. For example, rapid heating ofcells using HIFU may be advantageous for rapidly attenuating aninfectious activity by inducing cell death as opposed to slow increasesin temperature to which the cells may become adapted. See, e.g.,Somwaru, et al., J. Androl. 25:506-513, 2004 (the contents of which areincorporated herein by reference); Stankiewicz, et al., J. Biol. Chem.280:38729-38739, 2005 (the contents of which are incorporated herein byreference); Sodja, et al., J. Cell Sci. 111:2305-2313, 1998 (thecontents of which are incorporated herein by reference); Setroikromo, etal., Cell Stress Chaperones 12:320-330, 2007 (the contents of which areincorporated herein by reference); Dubinsky, et al., AJR 190:191-199,2008 (the contents of which are incorporated herein by reference);Lepock. Int. J. Hyperthermia, 19:252-266, 2003 (the contents of whichare incorporated herein by reference); Roti Roti Int. J. Hyperthermia24:3-15, 2008 (the contents of which are incorporated herein byreference); Fuchs, et al., “The Laser's Position in Medicine” pp 187-198in Applied Laser Medicine. Ed. Hans-Peter Berlien, Gerhard J. Muller,Springer-Verlag New York, LLC, 2003 (the contents of which areincorporated herein by reference).

In an embodiment, an implantable device 102 includes a sensor component902 configured to perform a real-time comparison of a measurandassociated with a biological sample proximate one or more regions of atleast one surface of the implantable device 102 to stored referencedata. The implantable device 102 can include, among other things, one ormore energy emitters 302 configured to emit a pulsed thermal sterilizingstimulus of a character and for a time sufficient to induce PCD withoutsubstantially inducing necrosis of at least a portion of cells proximatethe implantable device 102 in response to the comparison. In anembodiment, at least one of the one or more energy emitters 302 isconfigured to emit a pulsed thermal sterilizing stimulus of a characterand for a time sufficient to induce PCD without substantially inducingnecrosis of an infectious agent within a tissue proximate theimplantable device 102 in response to a detect level of an infectiousagent.

In an embodiment, at least one of the one or more energy emitters 302 isconfigured to emit a pulsed thermal sterilizing stimulus of a characterand for a duration sufficient to induce PCD without substantiallyinducing necrosis of a pathogen within a region proximate theimplantable device 102. In an embodiment, at least one of the one ormore energy emitters 302 is configured to deliver a pulsed thermalsterilizing stimulus of a character and for a duration sufficient toinduce thermal poration of a plasma membrane in at least a portion ofcells within a tissue proximate the implantable device 102. In anembodiment, at least of the one or more energy emitters 302 isconfigured to deliver a pulsed thermal sterilizing stimulus of acharacter and for a time sufficient to induce poration of a plasmamembrane in at least a portion of cells on a surface of the implantabledevice 102.

In an embodiment, the one or more energy emitters 302 are operable toemit a sufficient amount of a pulsed thermal sterilizing stimulus toincrease the temperature of at least a portion of cells proximate theimplantable device 102 by about 3° C. to about 22° C. In an embodiment,the one or more energy emitters 108 are operable to emit a sufficientamount of a pulsed thermal sterilizing stimulus to increase thetemperature of at least a portion of cells proximate the indwellingmedical implant 102 by about 3° C. to about 10° C. In an embodiment, theone or more energy emitters 302 are operable to emit a sufficient amountof a pulsed thermal sterilizing stimulus to increase the temperature ofat least a portion of cells proximate the implantable device 102 byabout 3° C. to about 4° C. In an embodiment, at least one of the one ormore energy emitters 302 is configured to deliver a pulsed thermalsterilizing stimulus of a character and for a duration sufficient toelevate a temperature of at least a portion of cells proximate theimplantable device 102 from about 37° C. to less than about 60° C. In anembodiment, at least one of the one or more energy emitters 302 isconfigured to deliver a pulsed thermal sterilizing stimulus of acharacter and for a duration sufficient to elevate a temperature of atleast a portion of cells proximate the indwelling medical implant fromabout 37° C. to less than about 47° C. In an embodiment, at least one ofthe one or more energy emitters 108 is configured to deliver a pulsedthermal sterilizing stimulus 37° C. of a character and for a durationsufficient to elevate a temperature of at least a portion of cellsproximate the implantable device 102 from about 37° C. to less thanabout 45° C. In an embodiment, at least one of the one or more energyemitters 302 is configured to deliver a pulsed thermal sterilizingstimulus of a character and for a duration sufficient to elevate atemperature of at least a portion of cells proximate the implantabledevice 102 from about 37° C. to less than about 42° C. In an embodiment,least one of the one or more energy emitters 302 is configured todeliver a pulsed thermal sterilizing stimulus of a character and for aduration sufficient to elevate a temperature of at least a portion ofcells proximate the indwelling medical implant 102 from about 37° C. toa temperature ranging from greater than about 41° C. to less than about63° C.

In an embodiment, the system 100 includes, among other things, a bodystructure 104 having a surface defining one or more fluid-flowpassageways configured to receive a biological fluid of a biologicalsubject, and one or more energy emitters 302 configured to emit a pulsedthermal sterilizing stimulus of a character and for a time sufficient toinduce PCD without substantially inducing necrosis of at least a portionof cells within the biological fluid proximate the surface of the bodystructure 104 in response to a determination that an infectious agent ispresent within the biological fluid.

In an embodiment, the one or more energy emitters 302 are configure toemit a sufficient amount of a pulsed thermal sterilizing stimulus toincrease the temperature of at least a portion of a cerebrospinal fluidreceived within at least one of the one or more fluid-flow passagewaysby about 3° C. to about 22° C. In an embodiment, the one or more energyemitters 302 are configure to emit a sufficient amount of a pulsedthermal sterilizing stimulus to increase the temperature of at least aportion of a cerebrospinal fluid received within at least one of the oneor more fluid-flow passageways by about 3° C. to about 10° C. In anembodiment, the one or more energy emitters 302 are configure to emit asufficient amount of a pulsed thermal sterilizing stimulus to increasethe temperature of at least a portion of cells within a cerebrospinalfluid received within at least one of the one or more fluid-flowpassageways by about 3° C. to about 4° C.

In an embodiment, at least one of the one or more energy emitters 302 isconfigured to deliver a pulsed thermal sterilizing stimulus of acharacter and for a duration sufficient to elevate a temperature atleast a portion of cells within a cerebrospinal fluid received within atleast one of the one or more fluid-flow passageways from about 37° C. toless than about 60° C. In an embodiment, at least one of the one or moreenergy emitters 302 is configured to deliver a pulsed thermalsterilizing stimulus of a character and for a duration sufficient toelevate a temperature at least a portion of cells within a cerebrospinalfluid received within at least one of the one or more fluid-flowpassageways from about 37° C. to less than about 47° C. In anembodiment, at least one of the one or more energy emitters 302 isconfigured to deliver a pulsed thermal sterilizing stimulus of acharacter and for a duration sufficient to elevate a temperature of atleast a portion of cells within a cerebrospinal fluid received within atleast one of the one or more fluid-flow passageways from about 37° C. toless than about 45° C. In an embodiment, at least one of the one or moreenergy emitters 302 is configured to deliver a pulsed thermalsterilizing stimulus of a character and for a duration sufficient toelevate a temperature of at least a portion of cells within acerebrospinal fluid received within at least one of the one or morefluid-flow passageways from about 37° C. to less than about 42° C. In anembodiment, at least one of the one or more energy emitters 302 isconfigured to deliver a pulsed thermal sterilizing stimulus of acharacter and for a duration sufficient to elevate temperature of atleast a portion of cells within a cerebrospinal fluid received within atleast one of the one or more fluid-flow passageways from about a normalbody temperature to a temperature ranging from greater than about 41° C.to less than about 63° C.

In an embodiment, at least one of the one or more energy emitters 302 isconfigured to emit a pulsed thermal sterilizing stimulus of a characterand for a time sufficient to induce PCD without substantially inducingnecrosis of an infectious agent within a cerebrospinal fluid proximatethe surface of the body structure 104. In an embodiment, at least one ofthe one or more energy emitters 302 is configured to emit an energystimulus of a character and for a time sufficient to induce PCD withoutsubstantially inducing necrosis of a pathogen within a cerebrospinalproximate the surface of the body structure 104.

In an embodiment, the body structure 104 includes one or morecerebrospinal fluid shunts configured to drain cerebrospinal fluid froma region of a brain of the biological subject. In an embodiment, thebody structure 104 includes one or more cannulas configured to drain acerebrospinal fluid from a ventricle of a brain of the biologicalsubject. In an embodiment, the body structure 104 includes aventriculoperitoneal shunt.

The system 100 can include, but is not limited to, one or moreelectromagnetic energy emitters 328. In an embodiment, the implantabledevice 102 includes one or more electromagnetic energy emitters 328. Inan embodiment, the one or more electromagnetic energy emitters 328 areconfigured to provide a voltage across at least a portion of cellsproximate an outer surface 108 of the implantable device 102. In anembodiment, the one or more electromagnetic energy emitters 328 includeone or more electrodes 330. In an embodiment, the one or moreelectromagnetic energy emitters 328 include one or more light-emittingdiodes 310. In an embodiment, the one or more electromagnetic energyemitters 328 include at least one electron emitting material.

In an embodiment, the one or more electromagnetic energy emitters 328are configured to provide a voltage across at least a portion of tissueproximate the implantable device 102, and to induce pore formation in aplasma membrane of at least a portion of infectious agents within aregion proximate the implantable device 102. In an embodiment, thevoltage is of sufficient strength or duration to exceed a nominaldielectric strength of at least one cell plasma membrane. In anembodiment, the one or more electromagnetic energy emitters 328 areconfigured to provide a voltage across at least a portion of cellswithin a biological fluid received within at least one of the one ormore fluid-flow passageways 106. In an embodiment, the voltage is ofsufficient strength and duration to exceed a nominal dielectric strengthof at least one cell plasma membrane. In an embodiment, the voltage isof sufficient strength and duration to exceed a nominal dielectricstrength of a cell plasma membrane without substantially interferingwith a normal operation of the implantable shunt system.

The system 100 can include, but is not limited to, one or moreelectrical energy emitters 332. In an embodiment, the implantable device102 includes one or more electrical energy emitters 332. In anembodiment, the one or more electrical energy emitters 326 include atleast one electrode 330. In an embodiment, a plurality of electrodes 330are configured to energize a region proximate the implantable device 102in the presence of an applied potential. In an embodiment, the appliedpotential is sufficient to produce superoxidized water from an aqueoussalt composition proximate the plurality of electrodes 330. In anembodiment, the applied potential is sufficient to produce at least oneof a triplet excited-state specie, a reactive oxygen specie, a reactivenitrogen specie, a free radical, a peroxide, and any other inorganic ororganic ion and molecules that include oxygen ions.

In an embodiment, a plurality of electrodes 330 are configured toprovide an electrical energy stimulus. Electrodes 330 can take a varietyof forms, configurations, and geometrical patterns including forexample, but not limited to, a one-, two-, or three-dimensional arrays,a pattern comprising concentric geometrical shapes, a pattern comprisingrectangles, squares, circles, triangles, polygons, any regular orirregular shapes, and the like, and any combination thereof. Techniquessuitable for making patterned electrodes include, but are not limitedto, electro-deposition, electro-deposition onto laser-drilled polymermolds, laser cutting and electro-polishing, laser micromachining,surface micro-machining, soft lithography, x-ray lithography, LIGAtechniques (e.g., X-ray lithography, electroplating, and molding),conductive paint silk screen techniques, conventional patteringtechniques, injection molding, conventional silicon-based fabricationmethods (e.g., inductively coupled plasma etching, wet etching,isotropic and anisotropic etching, isotropic silicon etching,anisotropic silicon etching, anisotropic GaAs etching, deep reactive ionetching, silicon isotropic etching, silicon bulk micromachining, or thelike), complementary-symmetry/metal-oxide semiconductor (CMOS)technology, deep x-ray exposure techniques, and the like.

In an embodiment, the one or more energy emitters 302 deliver an energystimulus to a biological fluid received within the one or morefluid-flow passageways 106. In an embodiment, the one or more energyemitters 302 deliver an emitted energy stimulus to a biological fluidproximate a surface of implantable device 102. In an embodiment, the oneor more energy emitters 302 deliver an energy stimulus along asubstantially longitudinal direction of at least one of the one or morefluid-flow passageways 106. In an embodiment, the one or more energyemitters 302 deliver an energy stimulus along a substantially lateraldirection of at least one of the one or more fluid-flow passageways 106.In an embodiment, the one or more energy emitters 302 deliver a firstportion of an emitted energy stimulus along a substantially lateraldirection in one or more regions of at least one of the one or morefluid-flow passageways 106 and deliver a second portion of the emittedenergy stimulus along a substantially longitudinal direction in one ormore regions of at least one of the one or more fluid-flow passageways106. In an embodiment, the one or more energy emitters 302 deliver atleast a portion of an emitted energy stimulus along a substantiallylateral direction in a first region of at least one of the one or morefluid-flow passageways 106 and deliver at least a portion of the emittedenergy stimulus along a substantially lateral direction in a secondregion of the one or more fluid-flow passageways 106, the second regiondifferent from the first region. In an embodiment, the one or moreenergy emitters 302 deliver at least a portion of an emitted energystimulus along a substantially longitudinal direction in a first regionof at least one of the one or more fluid-flow passageways 106 anddeliver at least a portion of the emitted energy stimulus along asubstantially longitudinal direction in a second region of the one ormore fluid-flow passageways 106, the second region different from thefirst region. In an embodiment, the one or more energy emitters 302deliver at least a portion of an emitted energy stimulus along asubstantially lateral direction in a first region of at least one of theone or more fluid-flow passageways 106 and at least a portion of theemitted energy stimulus along a substantially lateral direction in asecond region of the one or more fluid-flow passageways 106, the secondregion different from the first region.

The system 100 can include, but is not limited to, one or more spatiallypatterned energy emitters 334. The system 100 can include, but is notlimited to, one or more spaced-apart energy emitters 336. The system 100can include, but is not limited to, one or more patterned energyemitters 338. Patterned energy emitters 338 can be sized and shaped toprovide a spatially patterned energy stimulus to, for example, a regionproximate an implantable device 102. In an embodiment, a plurality ofenergy emitters 302 provide a spatially patterned energy stimulus. Thespatially patterned energy stimulus can take a variety forms,configurations, and geometrical patterns including for example, but notlimited to, lines, circles, ellipses, triangles, rectangles, polygons,any regular or irregular geometrical patterns, one-dimensional patterns,two-dimensional patterns, three-dimensional patterns, and the like, andany combination thereof. In an embodiment, a plurality of energyemitters 302 includes a patterned energy-emitting source. In anembodiment, at least one of the one or more energy emitters 302 includesat least one of a patterned electromagnetic energy-emitting source, apatterned electrical energy-emitting source, a patterned ultrasonicenergy-emitting source, and a patterned thermal energy-emitting source.In an embodiment, at least one of the one or more energy emitters 302includes a patterned electrode.

Referring to FIGS. 4A and 4B, in an embodiment, the one or more energyemitters 302 include a patterned energy emitter 480 having one or moreconductive traces 482 that are deposited, etched, or otherwise appliedto a substrate to form one or more patterned electrodes. For example,lithographic techniques can be used to form a conductive trace layout490, onto a surface of a substrate 486. The lithographic process forforming the conductive trace layouts 490 can include for example, butnot limited to, applying a resist film (e.g., spin-coating a photoresistfilm) onto the substrate, exposing the resist with an image of a circuitlayout (e.g., the geometric pattern of one or more conductive traces),heat treating the resist, developing the resist, transferring the layoutonto the substrate, and removing the remaining resist. Transferring thelayout onto the substrate 486 can include, but is not limited to, usingtechniques like subtractive transfer, etching, additive transfer,selective deposition, impurity doping, ion implantation, and the like.Referring to FIGS. 5A and 5B, in an embodiment, patterned energyemitters 500, 510 can include, but are not limited to, two or moreelectrodes 502, 504 forming a pattern. In an embodiment, A patternedenergy emitter 500 includes two or more electrodes 502, 504 separated byan insulating material 506. In an embodiment, the patterned energyemitter 500 delivers an energy stimulus of a character and for a timesufficient to provide a temporally controllable, spatially patterned,energy stimulus. In an embodiment, the patterned energy emitter 500delivers an energy stimulus of a character and for a time sufficient toprovide a spatial distribution-controllable spatially patterned energystimulus.

Referring to FIG. 6, in an embodiment, the one or more energy emitters302 are arranged to provide an illumination pattern 600 comprising atleast a first region 602 and a second region 604. In an embodiment, thesecond region 604 of the illumination pattern 600 comprises at least oneof an illumination intensity (I_(n)), an energy-emitting pattern, a peakemission wavelength (a_(n)), an ON-pulse duration (D_((ON)n)), anOFF-pulse duration (D_((OFF)n)), and a pulse frequency (a_(n)) differentfrom the first region 602. The one or more energy emitters 302 canprovide a spatially patterned sterilizing stimulus having a peakemission wavelength in at least one of an x-ray, an ultraviolet, avisible, an infrared, a near infrared, a terahertz, microwave, and aradio frequency spectrum, or combinations thereof, to at least a portionof tissue proximate an implantable device 102. In an embodiment, the oneor more energy emitters 302 provide a spatially patterned optical energystimulus. The implantable device 102 can include, but is not limited to,a patterned-light emitting source. In an embodiment, the patterned-lightemitting source is configured to provide a spatially patterned energystimulus to at least one of biological fluid and tissue proximate theimplantable device 102.

In an embodiment, at least one of the one or more energy emitters 302 isconfigured to provide a spatially patterned energy stimulus having atleast a first region and a second region 604 different from the firstregion 602. In an embodiment, the first 602 region comprises one of aspatially patterned electromagnetic energy stimulus, a spatiallypatterned electrical energy stimulus, a spatially patterned ultrasonicenergy stimulus, or a spatially patterned thermal energy stimulus, andthe second region 604 comprises a spatially patterned energy stimulusthat is different from that in first region 602; that is of a spatiallypatterned electromagnetic energy stimulus, a spatially patternedelectrical energy stimulus, a spatially patterned ultrasonic energystimulus, or a spatially patterned thermal energy stimulus. In anembodiment, the spatially patterned energy stimulus is adapted toprovide a voltage across at least a portion of cells of tissue proximatean outer surface 108 of the implantable device 102. In an embodiment,the spatially patterned energy stimulus is adapted to provide a voltageacross a region proximate the implantable device 102, and to inactivatean infectious agents present within the region. In an embodiment, thespatially patterned energy stimulus is adapted to provide a voltageacross at least a portion of tissue proximate the implantable device102, and to induce pore formation in a plasma membrane of at least aportion of infectious agents within the region. In an embodiment, thevoltage is of sufficient strength or duration to exceed a nominaldielectric strength of at least one cell plasma membrane.

In an embodiment, an energy emitter 302 is operably coupled to aplurality of waveguides 902 and is configured to deliver a multiplexenergy stimulus having, for example, two or more peak emissionwavelengths. In an embodiment, a multiplex energy stimulus can be routedto two or more waveguides 902 based on a wavelength, an intensity, aspectral power distribution, a waveguide-specific address, or the like.Once routed, the a plurality of waveguides 902 can deliver a spatiallypatterned energy stimulus having at least a first region and a secondregion 604 different from the first region 602 where the differencedepends on the selection rule (e.g., spectral power distribution,irradiance, peak power, intensity, phase, polarization, frequency,repetition rate, bandwidth, waveguide-specific address, or the like)used to route the energy stimulus.

With continued reference to FIG. 3, the system 100 can include, but isnot limited to, one or more controllers 402 such as a processor (e.g., amicroprocessor) 404, a central processing unit (CPU) 406, a digitalsignal processor (DSP) 408, an application-specific integrated circuit(ASIC) 410, a field programmable gate array (FPGA) 412, or the like, orany combinations thereof, and can include discrete digital or analogcircuit elements or electronics, or combinations thereof. The system 100can include, but is not limited to, one or more field programmable gatearrays 412 having a plurality of programmable logic components. Thesystem 100 can include, but is not limited to, one or more anapplication specific integrated circuits having a plurality ofpredefined logic components. In an embodiment, at least one controller402 is operably coupled to one or more energy emitters 302. In anembodiment, the system 100 includes one or more controllers 402configured to concurrently or sequentially operate multiple energyemitters 302.

In an embodiment, one or more controllers 402 are configured toautomatically control at least one waveform characteristic (e.g.,intensity, frequency, pulse intensity, pulse duration, pulse ratio,pulse repetition rate, or the like) associated with the delivery of oneor more energy stimuli. For example, pulsed waves can be characterizedby the fraction of time the energy stimulus is present over one pulseperiod. This fraction is called the duty cycle and is calculated bydividing the pulse time ON by the total time of a pulse period (e.g.,time ON plus time OFF). In an embodiment, a pulse generator 320 isconfigured to electronically generate pulsed periods and non-pulsed (orinactive) periods.

In an embodiment, the controller 402 is configured to control at leastone parameter associated with a delivery of the energy stimulus. In anembodiment, the controller 402 is configured to control at least oneparameter associated with a spatial illumination field modulation, aspatial illumination field intensity, or a spatial illumination deliverypattern. In an embodiment, the controller 402 is configured to controlat least one of an excitation intensity, an excitation frequency, anexcitation pulse frequency, an excitation pulse ratio, an excitationpulse intensity, an excitation pulse duration time, an excitation pulserepetition rate, an energy stimulus delivery regimen, an ON-rate, and anOFF-rate. In an embodiment, the system 100 includes at least oneprocessor 404 communicably coupled to at least one of the one or moreenergy emitters 302 and configured to control at least one of a durationtime, an amount of energy (e.g., a fluence, peak power, average power,operational fluence, or the like), a delivery schedule, a deliverypattern, an excitation amount, an excitation type, and a deliverylocation associated with the delivery of the energy stimulus.

In an embodiment, the implantable device 102 are, for example,wirelessly coupled to a controller 402 that communicates with theimplantable device 102 via wireless communication. Non-limiting examplesof wireless communication include optical connections, ultravioletconnections, infrared, BLUETOOTH®, Internet connections, radio, networkconnections, and the like. The system 100 can include, but is notlimited to, means for generating a response 460 based on a comparison,of a detected at least one of an emitted energy and a remitted energy toat least one heuristically determined parameter, including one or morecontrollers 402.

In an embodiment, the system 100 includes at least one controller 402operably coupled to the one or more energy emitters 302 and configuredto control at least one parameter associated with the delivery of theenergy stimulus. In an embodiment, the at least one controller 402 isconfigured to control at least one of a duration time, an amount ofenergy, an excitation amount, an excitation type, a delivery location,and a spatial-pattern stimulation configuration associated with thedelivery of the energy stimulus.

The system 100 can include, but is not limited to, one or more memories414 that, for example, store instructions or data, for example, volatilememory (e.g., Random Access Memory (RAM) 416, Dynamic Random AccessMemory (DRAM), or the like), non-volatile memory (e.g., Read-Only Memory(ROM) 418, Electrically Erasable Programmable Read-Only Memory (EEPROM),Compact Disc Read-Only Memory (CD-ROM), or the like), persistent memory,or the like. Further non-limiting examples of one or more memories 414include Erasable Programmable Read-Only Memory (EPROM), flash memory,and the like. The one or more memories 414 can be coupled to, forexample, one or more controllers 402 by one or more instruction, data,or power buses 420.

The system 100 can include, but is not limited to, one or more databases422. In an embodiment, a database 422 includes at least one ofinflammation indication parameter data, infection indication parameterdata, diseased tissue indication parameter data, and the like. In anembodiment, a database 422 includes at least one of absorptioncoefficient data, extinction coefficient data, scattering coefficientdata, and the like. In an embodiment, a database 422 includes at leastone of stored reference data such as infection marker data, inflammationmarker data, infective stress marker data, a systemic inflammatoryresponse syndrome data, sepsis marker data, and the like. In anembodiment, a database 422 includes information associated with adisease state of a biological subject. In an embodiment, a database 422includes measurement data. In an embodiment, a database 422 includes atleast one of psychosis state indication information, psychosis traitindication information, and predisposition for a psychosis indicationinformation. In an embodiment, a database 422 includes at least one ofinfection indication information, inflammation indication information,diseased state indication information, and diseased tissue indicationinformation. In an embodiment, a database 422 includes at least one ofcryptographic protocol information, regulatory compliance protocolinformation (e.g., FDA regulatory compliance protocol information, orthe like), regulatory use protocol information, authentication protocolinformation, authorization protocol information, delivery regimenprotocol information, activation protocol information, encryptionprotocol information, decryption protocol information, treatmentprotocol information, and the like. In an embodiment, a database 422includes at least one of energy stimulus control delivery information,energy emitter control information, power control information, and thelike.

In an embodiment, the system 100 is configured to compare an inputassociated with at least one characteristic associated with a biologicalsubject to a database 422 of stored reference values, and to generate aresponse based in part on the comparison. In an embodiment, the system100 is configured to compare an input associated with at least onephysiological characteristic associated with a biological subject to adatabase 422 of stored reference values, and to generate a responsebased in part on the comparison.

In an embodiment, the at least one characteristic associated with abiological subject includes real-time detected information associatedwith tissue or biological fluid proximate an implantable device 102. Inan embodiment, the at least one characteristic associated with abiological subject includes real-time detected information associatedwith a biological fluid received within one or more fluid-flowpassageways 106. In an embodiment, the system 100 is configured tocompare an input associated with at least one characteristic associatedwith a biological fluid received within one or more fluid-flowpassageways 106 to a database 422 of stored reference values, and togenerate a response based in part on the comparison.

In an embodiment, the response includes at least one of a visualrepresentation, an audio representation (e.g., an alarm, an audiowaveform representation of a tissue region, or the like), a hapticrepresentation, and a tactile representation (e.g., a tactile diagram, atactile display, a tactile graph, a tactile interactive depiction, atactile model (e.g., a multidimensional model of an infected tissueregion, or the like), a tactile pattern (e.g., a refreshable Brailledisplay), a tactile-audio display, a tactile-audio graph, or the like).In an embodiment, the response includes generating at least one of avisual, an audio, a haptic, and a tactile representation of at least oneof biological fluid spectral information, tissue spectral information,fat spectral information, muscle spectral information, bone spectralinformation, blood component spectral information, and the like. In anembodiment, the response includes generating at least one of a visual,an audio, a haptic, and a tactile representation of at least onephysical or biochemical characteristic associated with a biologicalsubject.

In an embodiment, the response includes initiating one or more treatmentprotocols. In an embodiment, the response includes initiating at leastone treatment regimen. In an embodiment, the response includesdelivering an energy stimulus. In an embodiment, the response includesdelivering an active agent. In an embodiment, the response includesconcurrently or sequentially delivering an energy stimulus and an activeagent.

In an embodiment, the response includes at least one of a responsesignal, a control signal, a change to a sterilizing stimulus parameter(e.g., an electrical sterilizing stimulus, an electromagneticsterilizing stimulus, an ultrasonic sterilizing stimulus, or a thermalsterilizing stimulus), and the like. In an embodiment, the responseincludes at least one of a change in an excitation intensity, a changein an excitation frequency, a change in an excitation pulse frequency, achange in an excitation pulse ratio, a change in an excitation pulseintensity, a change in an excitation pulse duration time, a change in anexcitation pulse repetition rate, and the like.

In an embodiment, the response includes at least one of a change to asterilizing stimulus spatial pattern parameter (e.g., an electricalsterilizing stimulus spatial pattern parameter, an electromagneticsterilizing stimulus spatial pattern parameter, an ultrasonicsterilizing stimulus spatial pattern parameter, or a thermal sterilizingstimulus spatial pattern parameter), and a change in a sterilizingstimulus delivery regiment parameter (e.g., an electrical sterilizingstimulus delivery regiment parameter, an electromagnetic sterilizingstimulus delivery regiment parameter, an ultrasonic sterilizing stimulusdelivery regiment parameter, or a thermal sterilizing stimulus deliveryregiment parameter), or the like.

In an embodiment, the response includes at least one of activating anauthorization protocol, activating an authentication protocol,activating a software update protocol, activating a data transferprotocol, and activating an infection sterilization diagnostic protocol.In an embodiment, the response includes sending information associatedwith at least one of an authentication protocol, an authorizationprotocol, a delivery protocol, an activation protocol, an encryptionprotocol, and a decryption protocol.

In an embodiment, a database 422 includes at least one of storedreference data such as characteristic biological fluid (e.g.,cerebrospinal fluid) component signature data, characteristic bloodcomponent signature data, characteristic tissue signature data, and thelike. In an embodiment, a database 422 includes information indicativeof one or more spectral events associated with transmitted opticalenergy or a remitted optical energy from at least one of a biologicaltissue and biological fluid.

In an embodiment, a database 422 includes at least one of cerebrospinalfluid spectral information, blood spectral information, tissue spectralinformation, fat spectral information, muscle spectral information, andbone spectral information. In an embodiment, a database 422 includes atleast one of modeled tissue (e.g., blood, bone, muscle, tendons, organs,fluid-filled cysts, ventricles, or the like) spectral information ormodeled biological fluid spectral information. In an embodiment, adatabase 422 includes at least one of modeled biological fluid spectralinformation, modeled blood spectral information, modeled fat spectralinformation, modeled muscle spectral information, and modeled bonespectral information.

In an embodiment, a database 422 includes at least one of inflammationindication parameter data, infection indication parameter data, diseasedtissue indication parameter data, or the like. In an embodiment, adatabase 422 includes at least one of absorption coefficient data,extinction coefficient data, scattering coefficient data, and the like.In an embodiment, a database 422 includes stored reference data such ascharacteristic spectral signature data. In an embodiment, a database 422includes stored reference data such as infection marker data,inflammation marker data, infective stress marker data, a systemicinflammatory response syndrome data, sepsis marker data, or the like. Inan embodiment, a database 422 includes information associated with adisease state of a biological subject. In an embodiment, a database 422includes measurement data.

In an embodiment, the system 100 is configured to compare an inputassociated with a biological subject to a database 422 of storedreference values, and to generate a response based in part on thecomparison. In an embodiment, the system 100 is configured to compare anoutput of one or more of the plurality of logic components and todetermine at least one parameter associated with a cluster centroiddeviation derived from the comparison. In an embodiment, the system 100is configured to compare a measurand associated with the biologicalsubject to a threshold value associated with a spectral model and togenerate a response based on the comparison. In an embodiment, thesystem 100 is configured to generate the response based on thecomparison of a measurand that modulates with a detected heart beat ofthe biological subject to a target value associated with a spectralmodel.

In an embodiment, the system 100 is configured to compare the measurandassociated with the biological subject to the threshold value associatedwith a spectral model and to generate a real-time estimation of theformation of an obstruction of a flow in a fluid-flow passageway 106based on the comparison. In an embodiment, the system 100 is configuredto compare an input associated with at least one characteristicassociated with, for example, a tissue proximate an implantable device102 to a database 422 of stored reference values, and to generate aresponse based in part on the comparison.

The system 100 can include, but is not limited to, one or more datastructures (e.g., physical data structures) 424. In an embodiment, adata structure 424 includes information associated with at least oneparameter associated with a tissue water content, an oxy-hemoglobinconcentration, a deoxyhemoglobin concentration, an oxygenated hemoglobinabsorption parameter, a deoxygenated hemoglobin absorption parameter, atissue light scattering parameter, a tissue light absorption parameter,a hematological parameter, a pH level, or the like. The system 100 caninclude, but is not limited to, at least one of inflammation indicationparameter data, infection indication parameter data, diseased tissueindication parameter data, and the like configured as a data structure424. In an embodiment, a data structure 424 includes informationassociated with least one parameter associated with a cytokine plasmaconcentration or an acute phase protein plasma concentration. In anembodiment, a data structure 424 includes information associated with adisease state of a biological subject. In an embodiment, a datastructure 424 includes measurement data. In an embodiment, thecontroller 402 includes a processor 404 configured to executeinstructions, and a memory 414 that stores instructions configured tocause the processor 404 to generate a second response from informationencoded in a data structure 424.

The system 100 can include, but is not limited to, one or morecomputer-readable memory media (CRMM) 426 having cerebrospinal fluidinformation configured as a data structure, the data structure 424including at least one of psychosis state marker information, psychosistrait marker information, and psychosis indication information. Thesystem 100 can include, but is not limited to, one or morecomputer-readable memory media 426 having cerebrospinal fluidinformation configured as a data structure, the data structure 424including at least one of psychosis state indication information,psychosis trait indication information, and predisposition for apsychosis indication information. The system 100 can include, but is notlimited to, one or more computer-readable memory media 426 havingcerebrospinal fluid information configured as a data structure 424, thedata structure 424 including at least one of infection indicationinformation, inflammation indication information, diseased stateindication information, and diseased tissue indication information.

In an embodiment, a data structure 424 includes cerebrospinal fluidspectral information. In an embodiment, the cerebrospinal fluid spectralinformation includes one or more heuristically determined parametersassociated with at least one in vivo or in vitro determined metric. Forexample, information associated with cerebrospinal fluid components canbe determined by one or more in vivo or in vitro technologies ormethodologies including, for example, high resolution proton magneticresonance spectroscopy, nanoprobe nuclear magnetic resonancespectroscopy, in vivo micro-dialysis, flow cytometry, or the like.Non-limiting examples of heuristics include a heuristic protocol,heuristic algorithm, threshold information, a threshold level, a targetparameter, or the like. The system 100 can include, but is not limitedto, a means for generating one or more heuristically determinedparameters associated with at least one in vivo or in vitro determinedmetric including one or more data structures 424. The system 100 caninclude, but is not limited to, a means for generating a response basedon a comparison, of a detected at least one of an emitted energy and aremitted energy to at least one heuristically determined parameter,including one or more data structures 424.

In an embodiment, a data structure 424 includes one or more heuristics.In an embodiment, the one or more heuristics include a heuristic fordetermining a rate of change associated with at least one physicalparameter associated with a biological fluid. In an embodiment, the oneor more heuristics include a heuristic for determining the presence ofan infectious agent. In an embodiment, the one or more heuristicsinclude a heuristic for determining at least one dimension of aninfected tissue region. In an embodiment, the one or more heuristicsinclude a heuristic for determining a location of an infection. In anembodiment, the one or more heuristics include a heuristic fordetermining a rate of change associated with a biochemical marker withinthe one or more fluid-flow passageways 106. In an embodiment, the one ormore heuristics include a heuristic for determining a biochemical markeraggregation rate. In an embodiment, the one or more heuristics include aheuristic for determining a type of biochemical marker. In anembodiment, the one or more heuristics include a heuristic forgenerating at least one initial parameter. In an embodiment, the one ormore heuristics include a heuristic for forming an initial parameter setfrom one or more initial parameters. In an embodiment, the one or moreheuristics include a heuristic for generating at least one initialparameter, and for forming an initial parameter set from the at leastone initial parameter. In an embodiment, the one or more heuristicsinclude at least one pattern classification and regression protocol.

In an embodiment, a data structure 424 includes information associatedwith at least one parameter associated with a tissue water content, anoxy-hemoglobin concentration, a deoxyhemoglobin concentration, anoxygenated hemoglobin absorption parameter, a deoxygenated hemoglobinabsorption parameter, a tissue light scattering parameter, a tissuelight absorption parameter, a hematological parameter, a pH level, orthe like. The system 100 can include, but is not limited to, at leastone of inflammation indication parameter data, infection indicationparameter data, diseased tissue indication parameter data, and the likeconfigured as a data structure 424. In an embodiment, a data structure424 includes information associated with least one parameter associatedwith a cytokine plasma concentration or an acute phase protein plasmaconcentration. In an embodiment, a data structure 424 includesinformation associated with a disease state of a biological subject. Inan embodiment, a data structure 424 includes measurement data.

The system 100 can include, but is not limited to, one or morecomputer-readable media drives 426, interface sockets, Universal SerialBus (USB) ports, memory card slots, and the like, and one or moreinput/output components 428 such as, for example, a graphical userinterface 430, a display, a keyboard 432, a keypad, a trackball, ajoystick, a touch-screen, a mouse, a switch, a dial, and the like, andany other peripheral device. In an embodiment, the system 100 includesone or more user input/output components 428 that operably couple to atleast one controller 402 to control (electrical, electromechanical,software-implemented, firmware-implemented, or other control, orcombinations thereof) at least one parameter associated with the energydelivery associated with the one or more energy emitters 302. The system100 can include, but is not limited to, one or more modules optionallyoperable for communication with one or more input/output components 428that are configured to relay user output and/or input. In an embodiment,a module includes one or more instances of electrical,electromechanical, software-implemented, firmware-implemented, or othercontrol devices. Such device include one or more instances of memory414, controllers 402, ports, valves 132, antennas, power, or othersupplies; logic modules or other signaling modules; gauges or other suchactive or passive detection components; or piezoelectric transducers,shape memory elements, micro-electro-mechanical system (MEMS) elements,or other actuators.

The computer-readable media drive 426 or memory slot can be configuredto accept signal-bearing medium (e.g., computer-readable memory media,computer-readable recording media, or the like). In an embodiment, aprogram for causing the system 100 to execute any of the disclosedmethods can be stored on, for example, a computer-readable recordingmedium (CRMM) 434, a signal-bearing medium, and the like. Non-limitingexamples of signal-bearing media include a recordable type medium suchas a magnetic tape, floppy disk, a hard disk drive, a Compact Disc (CD),a Digital Video Disk (DVD), Blu-Ray Disc, a digital tape, a computermemory, or the like, as well as transmission type medium such as adigital and/or an analog communication medium (e.g., a fiber opticcable, a waveguide, a wired communications link, a wirelesscommunication link (e.g., transmitter, receiver, transmission logic,reception logic, etc.), etc.). Further non-limiting examples ofsignal-bearing media include, but are not limited to, DVD-ROM, DVD-RAM,DVD+RW, DVD-RW, DVD-R, DVD+R, CD-ROM, Super Audio CD, CD-R, CD+R, CD+RW,CD-RW, Video Compact Discs, Super Video Discs, flash memory, magnetictape, magneto-optic disk, MINIDISC, non-volatile memory card, EEPROM,optical disk, optical storage, RAM, ROM, system memory, web server, andthe like.

In an embodiment, the system 100 includes signal-bearing media in theform of one or more logic devices (e.g., programmable logic devices,complex programmable logic device, field-programmable gate arrays,application specific integrated circuits, or the like) comprising, forexample, a data structure 424 including one or more look-up tables. Thesystem 100 can include, but is not limited to, signal-bearing mediahaving biological fluid information configured as a data structure 424.In an embodiment, the data structure 424 includes at least one ofpsychosis state indication information, psychosis trait indicationinformation, and predisposition for a psychosis indication information.In an embodiment, the data structure 424 includes at least one ofinfection indication information, inflammation indication information,diseased state indication information, and diseased tissue indicationinformation.

The system 100 can include, but is not limited to, at least one sensorcomponents 440 including one or more sensors 442. In an embodiment, thesensor component 440 is configured to detect (e.g., assess, calculate,evaluate, determine, gauge, measure, monitor, quantify, resolve, sense,or the like) at least one characteristic (e.g., a spectralcharacteristic, a spectral signature, a physical quantity, anenvironmental attribute, a physiologic characteristic, or the like)associated with a biological subject. In an embodiment, the sensorcomponent 440 is in optical communication along an optical path with atleast one of the one or more energy emitters 302.

In an embodiment, the sensor component 440 is configured to detectspectral information associated with a real-time change in one or moreparameters associated with a biological fluid. For example, in anembodiment, the sensor component 440 is configured to detect at leastone of an emitted energy and a remitted energy associated with areal-time change in one or more parameters associated with a biologicalfluid. In an embodiment, the system 100 includes means for detecting atleast one characteristic associated with a biological subject includingat least one sensor component 440 having one or more sensors 442 and atleast one controller 402 operably coupled to the at least one sensorcomponent 440.

In an embodiment, the at least one characteristic associated with abiological subject includes a characteristic associated with tissueproximate the implantable. In an embodiment, the at least onecharacteristic associated with a biological subject includes acharacteristic associated with a biological fluid of the biologicalsubject. In an embodiment, the at least one characteristic associatedwith a biological subject includes a physiological characteristic of thebiological subject. In an embodiment, the at least one characteristicassociated with a biological subject includes a characteristicassociated with a cerebrospinal fluid of the biological subject. In anembodiment, the at least one characteristic associated with a biologicalsubject includes a characteristic associated with a tissue of thebiological subject. In an embodiment, the at least one characteristicassociated with a biological subject includes a specimen of thebiological subject. In an embodiment, the at least one characteristicassociated with a biological subject includes one or more spectroscopicproperties (e.g., tissue spectroscopic properties, biological fluidspectroscopic properties, infectious agent spectroscopic properties,biomarker spectroscopic properties, or the like). In an embodiment, theat least one characteristic associated with a biological subjectincludes at least one characteristic (e.g., a spectral characteristic, aspectral signature, a physical quantity, a relative quantity, anenvironmental attribute, a physiologic characteristic, or the like)associated with a region within the biological subject. In anembodiment, the at least one characteristic associated with a biologicalsubject includes a characteristic associated with a fluid-flowpassageway 106 obstruction, a hematological abnormality, or a body fluidflow abnormality (e.g., a cerebrospinal fluid abnormality). In anembodiment, the at least one characteristic associated with a biologicalsubject includes a characteristic associated with a biological fluidflow vessel. In an embodiment, the at least one characteristicassociated with a biological subject includes a characteristicassociated with one or more cerebrospinal fluid components. In anembodiment, the at least one characteristic associated with a biologicalsubject includes a characteristic associated with one or more imagingprobes attached, targeted to, conjugated, bound, or associated with atleast one inflammation markers. In an embodiment, the at least onecharacteristic associated with a biological subject includes acharacteristic associated with one or more imaging probes attached,targeted to, conjugated, bound, or associated with at least one bloodcomponents. In an embodiment, the at least one characteristic associatedwith a biological subject includes a characteristic associated with oneor more blood components. In an embodiment, the at least onecharacteristic associated with a biological subject includes acharacteristic associated with one or more cerebrospinal fluidcomponents.

In an embodiment, one or more of the sensors 442 are configured todetermine at least one characteristic associated with a biological fluidreceived within one or more fluid-flow passageways 106. In anembodiment, one or more of the sensors 442 are configured to detect atleast one of a characteristic of a biological fluid proximate theimplantable device 102, a characteristic of a tissue proximate theimplantable device 102, and a physiological characteristic of thebiological subject.

In an embodiment, one or more of the sensors 442 are configured todetect at least one physiological characteristic associated with abiological subject. For example, physiological characteristics such as,for example pH can be used to assess blood flow, a cell metabolic state(e.g., anaerobic metabolism, or the like), the presence of an infectiousagent, a disease state, and the like. In an embodiment, the implantabledevice 102 includes one or more sensors 442 configured to determine atleast one of a physiological characteristic of a biological subject, anda characteristic associated with a tissue proximate the implantabledevice 102. Among physiological characteristics examples include, butare not limited to, at least one of a temperature, a regional or localtemperature, a pH, an impedance, a density, a sodium ion level, acalcium ion level, a potassium ion level, a glucose level, a lipoproteinlevel, a cholesterol level, a triglyceride level, a hormone level, ablood oxygen level, a pulse rate, a blood pressure, an intracranialpressure, a respiratory rate, a vital statistic, and the like. In anembodiment, the at least one physiological characteristic includes atleast one of a temperature, a pH, an impedance, a density, a sodium ionlevel, a calcium ion level, a potassium ion level, a glucose level, alipoprotein level, a cholesterol level, a triglyceride level, a hormonelevel, a blood oxygen level, a pulse rate, a blood pressure, anintracranial pressure, and a respiratory rate.

In an embodiment, the at least one physiological characteristic includesat least one hematological parameter. In an embodiment, thehematological parameter is associated with a hematological abnormality.In an embodiment, the at least one physiological characteristic includesone or more parameters associated with at least one of leukopenia,leukophilia, lymphocytopenia, lymphocytophilia, neutropenia,neutrophilia, thrombocytopenia, disseminated intravascular coagulation,bacteremia, and viremia.

In an embodiment, the at least one physiological characteristic includesat least one of an infection marker, an inflammation marker, aninfective stress marker, a systemic inflammatory response syndromemarker, and a sepsis marker. In an embodiment, the infection markerincludes at least one of a red blood cell count, a lymphocyte level, aleukocyte count, a myeloid count, an erythrocyte sedimentation rate, anda C-reactive protein level. In an embodiment, the at least onephysiological characteristic includes at least one of a cytokine plasmaconcentration and an acute phase protein plasma concentration.

The implantable device 102 can include, but is not limited to, circuitryfor performing a comparison of the determined at least onecharacteristic associated with the tissue or a biological fluidproximate the implantable device 102 to stored reference data followingthe delivery of the energy stimulus. Circuitry can include one or morecomponents operably coupled (e.g., communicatively coupled,electromagnetically, magnetically, ultrasonically, optically,inductively, electrically, capacitively coupleable, or the like) to eachother. In an embodiment, circuitry can include one or more remotelylocated components. In an embodiment, remotely located components areoperably coupled via wireless communication. In an embodiment, remotelylocated components are operably coupled via one or more receivers,transmitters, transceivers, and the like.

The implantable device 102 can include, but is not limited to, circuitryconfigured to generate a response based at least in part on thecomparison. The implantable device 102 can include, but is not limitedto, one or more processors 404 configured to perform a comparison of theat least one characteristic associated with the tissue or a biologicalfluid proximate the implantable device 102 stored reference datafollowing delivery of the sterilizing stimulus, and to generate aresponse based at least in part on the comparison.

In an embodiment, the one or more energy emitters 302 are configured todirect an in vivo generated pulsed energy stimulus along an optical pathfor a time sufficient to interact with one or more regions within thebiological subject and for a time sufficient for a portion of the invivo generated pulsed energy stimulus to reach a portion of the sensorcomponent 440 that is in optical communication along the optical path.In an embodiment, the one or more energy emitters 302 are configured todirect optical energy along an optical path for a time sufficient tointeract with one or more regions within the biological subject and withat least a portion of the optical energy sensor component 440. In anembodiment, one or more of the energy emitters 302 are configured toemit a pulsed optical energy stimulus along an optical path for a timesufficient to interact with a cerebrospinal fluid received within theone or more fluid-flow passageways 106, such that a portion of thepulsed optical energy stimulus is directed to a portion of the sensorcomponent 440 that is in optical communication along the optical path.

In an embodiment, the sensor component 440 includes an imagingspectrometer. In an embodiment, the sensor component 440 comprises atleast one of a photo-acoustic imaging spectrometer, a thermo-acousticimaging spectrometer, and a photo-acoustic/thermo-acoustic tomographicimaging spectrometer. In an embodiment, optical energy sensor componentincludes at least one of a thermal detector, a photovoltaic detector, ora photomultiplier detector. In an embodiment, the optical energy sensorcomponent includes at least one of a charge coupled device, acomplementary metal-oxide-semiconductor device, a photodiode imagesensor device, a Whispering Gallery Mode (WGM) micro cavity device, anda scintillation detector device.

In an embodiment, the sensor component 440 is configured to detect atleast one of an emitted energy and a remitted energy. In an embodiment,the sensor component 440 is configured to detect at least one of anemitted energy and a remitted energy associated with a biologicalsubject. In an embodiment, the sensor component 400 is configured todetect an optical energy absorption profile of a portion of a tissue orbiological fluid within the biological subject. In an embodiment, thesensor component 440 is configured to detect an excitation radiation andan emission radiation associated with a portion of a tissue orbiological fluid within a biological subject.

In an embodiment, the sensor component 440 is configured to detect atleast one of an energy absorption profile and an energy reflectionprofile of a region within a biological subject. The system 100 caninclude, but is not limited to, means for detecting at least one of anemitted energy and a remitted energy including an interrogation energysource and one or more sensor components 440 having one or more sensors442. In an embodiment, the sensor component 440 includes at least one ofa time-integrating optical component 444, a linear time-integratingcomponent 446, a nonlinear optical component 448, and a temporalautocorrelating component 450. In an embodiment, the sensor component440 includes one or more one-, two-, or three-dimensional photodiodearrays.

Among sensors 442 examples include, but are not limited to, acousticwave sensors, aptamer-based sensors, biosensors, blood volume pulsesensors, cantilevers, conductance sensors, electrochemical sensors,fluorescence sensors, force sensors, heat sensors (e.g., thermistors,thermocouples, or the like), high resolution temperature sensors,differential calorimeter sensors, optical sensors, goniometry sensors,potentiometer sensors, resistance sensors, respiration sensors, soundsensors (e.g., ultrasound), Surface Plasmon Band Gap sensor (SPRBG),physiological sensors, surface plasmon sensors, and the like. Furthernon-limiting examples of sensors include affinity sensors, bioprobes,biostatistics sensors, enzymatic sensors, in-situ sensors (e.g., in-situchemical sensor), ion sensors, light sensors (e.g., visible, infrared,or the like), microbiological sensors, microhotplate sensors,micron-scale moisture sensors, nanosensors, optical chemical sensors,single particle sensors, and the like. Further non-limiting examples ofsensors include chemical sensors, cavitand-based supramolecular sensors,nucleic acid sensors, deoxyribonucleic acid sensors (e.g.,electrochemical DNA sensors, or the like), supramolecular sensors, andthe like. In an embodiment, at least one of the one or more sensors 442is configured to detect or measure the presence or concentration ofspecific target chemicals (e.g., blood components, biological fluidcomponent, cerebral spinal fluid component, infectious agents, infectionindication chemicals, inflammation indication chemicals, diseased tissueindication chemicals, biological agents, molecules, ions, or the like).

Further non-limiting examples of the one or more sensors 442 includechemical transducers, ion sensitive field effect transistors (ISFETs),ISFET pH sensors, membrane-ISFET devices (MEMFET), microelectronicion-sensitive devices, potentiometric ion sensors, quadruple-functionChemFET (chemical-sensitive field-effect transistor) integrated-circuitsensors, sensors with ion-sensitivity and selectivity to different ionicspecies, and the like.

Further non-limiting examples of the one or more sensors 442 can befound in the following documents (the contents of which are incorporatedherein by reference): U.S. Pat. Nos. 7,396,676 (issued Jul. 8, 2008) and6,831,748 (issued Dec. 14, 2004).

In an embodiment, the one or more sensors 442 include one or moreelectrochemical transducers, photochemical transducer, opticaltransducers, piezoelectrical transducers, or thermal transducers. In anembodiment, the one or more sensors 442 include one or more thermaldetectors, photovoltaic detectors, or photomultiplier detectors. In anembodiment, the one or more sensors 442 include one or more chargecoupled devices, complementary metal-oxide-semiconductor devices,photodiode image sensor devices, whispering gallery mode micro cavitydevices, or scintillation detector devices. In an embodiment, the one ormore sensors 442 include one or more ultrasonic transducers 314. In anembodiment, the one or more sensors 442 include one or more conductivitysensor. In an embodiment, the one or more sensors 442 include one ormore spectrometers.

In an embodiment, the one or more sensors 442 include one or moredensity sensors. In an embodiment, the one or more density sensorsinclude one or more optical density sensors. In an embodiment, the oneor more density sensors include one or more refractive index sensors. Inan embodiment, the one or more refractive index sensors include one ormore fiber optic refractive index sensors.

In an embodiment, the one or more sensors 442 include one or moresurface plasmon resonance sensors. In an embodiment, the one or moresensors 442 include one or more localized surface plasmon resonancesensors. In an embodiment, surface plasmon resonance based sensorsdetect target molecules suspended in a fluid, for example, by reflectinglight off thin metal films in contact with the fluid. Adsorbingmolecules cause changes in the local index of refraction, resulting inchanges in the resonance conditions of the surface plasmon waves. In anembodiment, detection of target molecules includes monitoring shifts inthe resonance conditions of the surface plasmon waves due to changes inthe local index of refraction associates with adsorption of targetmolecules.

In an embodiment, the one or more sensors 442 include one or moreacoustic biosensors, amperometric biosensors, calorimetric biosensors,optical biosensors, or potentiometric biosensors. In an embodiment, theone or more sensors 442 include one or more fluid flow sensors. In anembodiment, the one or more sensors 442 include one or more differentialelectrodes. In an embodiment, the one or more sensors 442 include one ormore biomass sensors. In an embodiment, the one or more sensors 442include one or more immuno sensors.

In an embodiment, the one or more sensors 442 include one or morefunctionalized cantilevers. In an embodiment, the one or more sensors442 include a light transmissive support and a reflective metal layer.In an embodiment, the one or more sensors 442 include a biologicalmolecule capture layer. In an embodiment, the biological moleculecapture layer includes an array of different binding molecules thatspecifically bind one or more target molecules.

In an embodiment, the system 100 is configured to initiate one or moretreatment protocols. In an embodiment, the system 100 is configured toinitiate at least one treatment regimen based on a detected spectralevent. In an embodiment, the system 100 is configured to initiate atleast one treatment regimen based on a detected biomarker event. In anembodiment, the system 100 is configured to initiate at least onetreatment regimen based on a detected infection. In an embodiment, thesystem 100 is configured to initiate at least one treatment regimenbased on a detected cerebrospinal fluid pressure. In an embodiment, thesystem 100 is configured to initiate at least one treatment regimenbased on a detected a fluid vessel abnormalities (e.g., an obstruction),a detected biological fluid abnormality (e.g., cerebrospinal fluidabnormalities, hematological abnormalities, components concentration orlevel abnormalities, flow abnormalities, or the like), a detectedbiological parameter, or the like.

Many of the disclosed embodiments can be electrical, electromechanical,software-implemented, firmware-implemented, or other otherwiseimplemented, or combinations thereof. Many of the disclosed embodimentscan be software or otherwise in memory, such as one or more executableinstruction sequences or supplemental information as described herein.For example, in an embodiment, the implantable device 102 can include,but is not limited to, one or more controllers 402 configured to performa comparison of the at least one characteristic associated with thebiological subject to stored reference data, and to generate a responsebased at least in part on the comparison. In an embodiment, thegenerated response includes at least one of a response signal, a changeto a sterilizing stimulus parameter, a change in an excitationintensity, a change in an excitation frequency, a change in anexcitation pulse frequency, a change in an excitation pulse ratio, achange in an excitation pulse intensity, a change in an excitation pulseduration time, a change in an excitation pulse repetition rate, and achange in a sterilizing stimulus delivery regimen parameter.

The system 100 can include for example, but not limited to, one or moresensors 442 configured to determine at least one characteristicassociated with a biological fluid of the biological subject. In anembodiment, the one or more sensors 442 are configured to determine atleast one characteristic associated with a cerebrospinal fluid of thebiological subject. In an embodiment, the at least one characteristicassociated with the cerebrospinal fluid includes at least one of anautofluorescence, an immunofluorescence, and an indirectimmunofluorescence. In an embodiment, the at least one characteristicassociated with the cerebrospinal fluid includes flow or pressureinformation. In an embodiment, the at least one characteristicassociated with the cerebrospinal fluid includes at least one of anoptical density an opacity, and a refractivity. In an embodiment, the atleast one characteristic associated with the cerebrospinal fluidincludes at least one parameter associated with a psychosis state markeror a psychosis trait marker. In an embodiment, the at least onecharacteristic associated with the cerebrospinal fluid includes at leastone psychiatric disorder indication parameter. In an embodiment, the atleast one characteristic associated with the cerebrospinal fluidincludes at least one of an infection indication parameter, aninflammation indication parameter, a diseased state indication parameter(e.g., an absence, a presence, or a severity indication parameter), anda diseased tissue indication parameter.

In an embodiment, the at least one characteristic associated with thecerebrospinal fluid includes at least one of a psychotic disorderindication parameter, a psychotic state indication parameter, apsychotic trait indication parameter, a psychosis indication parameter,and a predisposition for a psychosis indication parameter. In anembodiment, the at least one characteristic associated with thecerebrospinal fluid includes at least one of a psychotic disorderindication, psychotic state indication, a psychotic trait indication, apsychosis indication, and a predisposition for a psychosis indication.

In an embodiment, at least one of the one or more sensors 442 isconfigured to detect a fluorescence associated with an autofluorescentmaterial within a cerebrospinal fluid received within at least one ofthe one or more fluid-flow passageways 106. In an embodiment, at leastone of the one or more sensors 442 is configured to detect anautofluorescence associated with monocytes within a cerebrospinal fluidreceived within at least one of the one or more fluid-flow passageways106. In an embodiment, at least one of the one or more sensors 442 isconfigured to detect an autofluorescence associated with amyloids withina cerebrospinal fluid received within at least one of the one or morefluid-flow passageways 106.

In an embodiment, the at least one characteristic associated with thecerebrospinal fluid includes at least one of an electromagnetic energyabsorption parameter, an energy stimulus emission parameter, an energystimulus scattering parameter, an energy stimulus reflectance parameter,an energy stimulus phase shift parameter, an energy stimulus dephasingparameter, and an energy stimulus depolarization parameter. In anembodiment, the at least one characteristic associated with thecerebrospinal fluid includes at least one of an electromagnetic energyabsorption parameter, an electromagnetic energy emission parameter, anelectromagnetic energy scattering parameter, an electromagnetic energyreflectance parameter, an electromagnetic energy phase shift parameter,an electromagnetic energy dephasing parameter, and an electromagneticenergy depolarization parameter. In an embodiment, the at least onecharacteristic associated with the cerebrospinal fluid includes at leastone of an absorbance, a reflectivity, and a transmittance. In anembodiment, the at least one characteristic associated with thecerebrospinal fluid includes at least one of a refraction and ascattering.

In an embodiment, the sensor component 440 is configured to detectspectral information associated with the cerebrospinal fluid. Forexample, In an embodiment, the sensor component 440 is configured todetect at least one of an absorption coefficient, an extinctioncoefficient, and a scattering coefficient associated with thecerebrospinal fluid. In an embodiment, the at least one characteristicassociated with the cerebrospinal fluid includes at least one of anabsorption coefficient, an extinction coefficient, and a scatteringcoefficient.

In an embodiment, the sensor component 440 is configured to detectspectral information associated with one or more cerebrospinal fluidcomponents. In an embodiment, the sensor component 440 is configured todetect an energy absorption of one or more cerebrospinal fluidcomponents. Non-limiting examples of detectable cerebrospinal fluidcomponents include adenosine deaminase, albumin, calcium, chloride,C-reactive protein, creatine kinase, creatinine, cystatin C, cytokines,glucose, hydrogencarbonate, immunoglobulin G, interleukins, lactate,lactate dehydrogenase, lipids, lymphocytes, monocytes, mononuclearcells, myelin basic protein, neuron-specific enolase, potassium,proteins, S-100 protein, small molecules, sodium, β₂-microglobulin, andthe like.

In an embodiment, at least one controller 402 is operably coupled to thesensor component 440 and configured to process an output associated withone or more sensors 442. In an embodiment, the system 100 includes oneor more controllers 402 configured to concurrently or sequentiallyoperate multiple sensors 442. In an embodiment, the system 100 includesone or more controllers 402 configured to perform a comparison of the atleast one characteristic associated with the cerebrospinal fluid tostored reference data, and to generate a response based at least in parton the comparison. In an embodiment, one or more of one or more sensors440 are configured to detect at least one of an emitted energy and aremitted energy, and to generate a response based on the detected atleast one of the emitted energy and the remitted energy.

In an embodiment, the system 100 includes a controller 402 operablycoupled to the one or more sensors 440 and configured to perform acomparison of at least one characteristic associated with thecerebrospinal fluid to stored reference data, and to generate a responsebased at least in part on the comparison. In an embodiment, the responseincludes at least one of a visual representation, an audiorepresentation, a haptic representation, and a tactile representation.In an embodiment, the response includes generating spectral informationassociated with a biological fluid component.

In an embodiment, the response includes a psychiatric disorderprobability score. In an embodiment, the generated response includes atleast one of a response signal, a control signal, a display, a change toan energy stimulus parameter, a change in an excitation intensity, achange in an excitation frequency, a change in an excitation pulsefrequency, a change in an excitation pulse ratio, a change in anexcitation pulse intensity, a change in an excitation pulse durationtime, a change in an excitation pulse repetition rate, or a change in anenergy stimulus delivery regimen parameter.

In an embodiment, one or more controllers 402 are configured toautomatically control one or more of a frequency, a duration, a pulserate, a duty cycle, or the like associated with an ultrasonic energygenerated by the one or more transducers 314 based on a sensedparameter. In an embodiment, one or more controllers 402 are configuredto automatically control one or more of a frequency, a duration, a pulserate, a duty cycle, or the like associated with the ultrasonic energygenerated by the one or more transducers 314 based on a sensed parameterassociated with a region within the biological subject.

The system 100 can include for example, but not limited to, one or moresensors 442 configured to determine at least one characteristicassociated with a biological specimen (e.g., biological fluid, tissue,or the like) proximate a surface (e.g., outer surface 108 or innersurface 110, or the like) of the implantable device 102. In anembodiment, the system 100 is configured to determine one or more tissuespectroscopic properties, such as, for example, a transport scatteringcoefficient or an absorption coefficient.

In an embodiment, the at least one characteristic associated with abiological specimen proximate a surface of the implantable device 102includes at least one of an inflammation indication parameter, aninfection indication parameter, a diseased state indication parameter,and a diseased tissue indication parameter. In an embodiment, the atleast one characteristic associated with a biological specimen proximatea surface of the implantable device 102 includes at least one of aninflammation indication parameter, an infection indication parameter, adiseased state indication parameter, and a diseased tissue indicationparameter. In an embodiment, the at least one characteristic associatedwith a biological specimen proximate a surface of the implantable device102 includes at least one parameter associated with an amount ofenergy-activatable disinfecting agent present in at least a portion ofthe tissue proximate a surface of the implantable device 102, a sodiumion content, a chloride content, a superoxide anion content, or ahydrogen peroxide content. In an embodiment, the at least onecharacteristic associated with a biological specimen proximate a surfaceof the implantable device 102 includes at least one of an absorptioncoefficient, an extinction coefficient, and a scattering coefficient.

In an embodiment, the at least one characteristic associated with abiological specimen proximate a surface of the implantable device 102includes at least one parameter associated with an infection marker, aninflammation marker, an infective stress marker, a systemic inflammatoryresponse syndrome marker, or a sepsis marker. In an embodiment, theinfection marker includes at least one of a red blood cell count, alymphocyte level, a leukocyte count, a myeloid count, an erythrocytesedimentation rate, and a C-reactive protein level.

In an embodiment, the at least one characteristic associated with abiological specimen proximate a surface of the implantable device 102includes at least one parameter associated with a tissue water content,an oxy-hemoglobin concentration, a deoxyhemoglobin concentration, anoxygenated hemoglobin absorption parameter, a deoxygenated hemoglobinabsorption parameter, a tissue light scattering parameter, a tissuelight absorption parameter, a hematological parameter, or a pH level. Inan embodiment, the at least one characteristic associated with abiological specimen proximate a surface of the implantable device 102includes at least one parameter associated with a cytokine plasmaconcentration or an acute phase protein plasma concentration. In anembodiment, the at least one characteristic associated with a biologicalspecimen proximate a surface of the implantable device 102 includes atleast one parameter associated with a leukocyte level. In an embodiment,the controller is communicatively coupled to the one or more sensors 442configured to determine the at least one characteristic associated witha biological specimen proximate a surface of the implantable device 102.

In an embodiment, one or more sensors 442 are configured to determine atleast one characteristic associated with a tissue proximate theimplantable device 102. In an embodiment, the at least onecharacteristic associated with the tissue proximate the implantabledevice 102 includes at least one of a transmittance, an energy stimulusfrequency change, energy stimulus frequency shift, an energy stimulusphase change, and energy stimulus phase shift. In an embodiment, the atleast one characteristic associated with the tissue proximate theimplantable device 102 includes at least one of a fluorescence, anintrinsic fluorescence, a tissue fluorescence, and a naturally occurringfluorophore fluorescence. In an embodiment, the at least onecharacteristic associated with the tissue proximate the implantabledevice 102 includes at least one of an electrical conductivity, andelectrical polarizability, and an electrical permittivity. In anembodiment, the at least one characteristic associated with the tissueproximate the implantable device 102 includes at least one of a thermalconductivity, a thermal diffusivity, a tissue temperature, and aregional temperature.

In an embodiment, the controller 402 is configured to perform acomparison of the at least one characteristic associated with the tissueproximate the at least one outer surface 108 to stored reference data,and to generate a response based at least in part on the comparison. Thesystem 100 can include for example, but not limited to, one or moreprocessors 404 configured to perform a comparison of the at least onecharacteristic associated with a biological specimen proximate a surfaceof the implantable device 102 to stored reference data, and to generatea response based at least in part on the comparison. In an embodiment,the system 100 is configured to compare an input associated with atleast one characteristic associated with a tissue proximate animplantable device 102 to a data structure 424 including referencevalues, and to generate a response based in part on the comparison. Inan embodiment, the system 100 is configured to compare an inputassociated with at least one physiological characteristic associatedwith a biological subject to a data structure 424 including referencevalues, and to generate a response based in part on the comparison. Inan embodiment, the system 100 is configured to compare an inputassociated with at least one characteristic associated with a tissueproximate an implantable device 102 to a data structure 424 includingreference values, and to generate a response based in part on thecomparison.

In an embodiment, the sensor component 440 is configured to detect atleast one of an emitted energy and a remitted energy associated with atissue of a biological subject. Blood is a tissue composed of, amongother components, formed elements (e.g., blood cells such aserythrocytes, leukocytes, thrombocytes, or the like) suspend in a matrix(plasma). The heart, blood vessels (e.g., arteries, arterioles,capillaries, veins, venules, or the like), and blood components, make upthe cardiovascular system. The cardiovascular system, among otherthings, moves oxygen, gases, and wastes to and from cells and tissues,maintains homeostasis by stabilizing body temperature and pH, and helpsfight diseases. In an embodiment, the sensor component 440 is configuredto detect at least one of an emitted energy and a remitted energyassociated with a portion of a cardiovascular system. In an embodiment,the sensor component 440 is configured to detect at least one of anemitted energy and a remitted energy associated with one or more bloodcomponents within a biological subject. In an embodiment, the sensorcomponent 440 is configured to detect at least one of an emitted energyand a remitted energy associated with one or more formed elements withina biological subject. In an embodiment, the sensor component 440 isconfigured to detect spectral information associated with one or more ofone or more blood components. In an embodiment, the sensor component 440is configured to detect at least one of an emitted energy and a remittedenergy associated with a real-time change in one or more parametersassociated with at least one blood component within a biologicalsubject. In an embodiment, the sensor component 440 is configured todetect an energy absorption of one or more blood components.

Non-limiting examples of detectable blood components includeerythrocytes, leukocytes (e.g., basophils, granulocytes, eosinophils,monocytes, macrophages, lymphocytes, neutrophils, or the like),thrombocytes, acetoacetate, acetone, acetylcholine, adenosinetriphosphate, adrenocorticotrophic hormone, alanine, albumin,aldosterone, aluminum, amyloid proteins (non-immunoglobulin),antibodies, apolipoproteins, ascorbic acid, aspartic acid, bicarbonate,bile acids, bilirubin, biotin, blood urea Nitrogen, bradykinin, bromide,cadmium, calciferol, calcitonin (ct), calcium, carbon dioxide,carboxyhemoglobin (as HbcO), cell-related plasma proteins,cholecystokinin (pancreozymin), cholesterol, citric acid, citrulline,complement components, coagulation factors, coagulation proteins,complement components, c-peptide, c-reactive protein, creatine,creatinine, cyanide, 11-deoxycortisol, deoxyribonucleic acid,dihydrotestosterone, diphosphoglycerate (phosphate), or the like.

Further non-limiting examples of detectable blood components include todopamine, enzymes, epidermal growth factor, epinephrine, ergothioneine,erythrocytes, erythropoietin, folic acid, fructose, furosemideglucuronide, galactoglycoprotein, galactose (children), gamma-globulin,gastric inhibitory peptide, gastrin, globulin, α-1-globulin,α-2-globulin, α-globulins, β-globulin, β-globulins, glucagon,glucosamine, glucose, immunoglobulins (antibodies), lipase p, lipids,lipoprotein (sr 12-20), lithium, low-molecular weight proteins, lysine,lysozyme (muramidase), α-2-macroglobulin, γ-mobility(non-immunoglobulin), pancreatic polypeptide, pantothenic acid,para-aminobenzoic acid, parathyroid hormone, pentose, phosphorated,phenol, phenylalanine, phosphatase, acid, prostatic, phospholipid,phosphorus, prealbumin, thyroxine-binding, proinsulin, prolactin(female), prolactin (male), proline, prostaglandins, prostate specificantigen, protein, protoporphyrin, pseudoglobulin I, pseudoglobulin II,purine, pyridoxine, pyrimidine nucleotide, pyruvic acid, CCL5 (RANTES),relaxin, retinol, retinol-binding protein, riboflavin, ribonucleic acid,secretin, serine, serotonin (5-hydroxytryptamine), silicon, sodium,solids, somatotropin (growth hormone), sphingomyelin, succinic acid,sugar, sulfates, inorganic, sulfur, taurine, testosterone (female),testosterone (male), triglycerides, triiodothyronine, tryptophan,tyrosine, urea, uric acid, water, miscellaneous trace components, andthe like.

Among γ-Globulins examples include, but are not limited to, α1-acidglycoprotein, α1-antichymotrypsin, α1-antitrypsin, α1B-glycoprotein,α1-fetoprotein, α1-microglobulin, α1T-glycoprotein, α2HS-glycoprotein,α2-macroglobulin, 3.1 S Leucine-rich α2-glycoprotein, 3.8 Shistidine-rich α2-glycoprotein, 4 S α2,α1-glycoprotein, 8 Sα3-glycoprotein, 9.5 S α1-glycoprotein (serum amyloid P protein),Corticosteroid-binding globulin, ceruloplasmin, GC globulin, haptoglobin(e.g., Type 1-1, Type 2-1, or Type 2-2), inter-α-trypsin inhibitor,pregnancy-associated α2-glycoprotein, serum cholinesterase,thyroxine-binding globulin, transcortin, vitamin D-binding protein,Zn-α2-glycoprotein, and the like. Among β-Globulins, examples include,but are not limited to, hemopexin, transferrin, β2-microglobulin,β2-glycoprotein I, β2-glycoprotein II, (C3 proactivator),β2-glycoprotein III, C-reactive protein, fibronectin, pregnancy-specificβ1-glycoprotein, ovotransferrin, and the like. Among immunoglobulinsexamples include, but are not limited to, immunoglobulin G (e.g., IgG,IgG₁, IgG₂, IgG₃, IgG₄), immunoglobulin A (e.g., IgA, IgA₁, IgA₂),immunoglobulin M, immunoglobulin D, immunoglobulin E, κ Bence Jonesprotein, γ Bence Jones protein, J Chain, and the like.

Among apolipoproteins examples include, but are not limited to,apolipoprotein A-I (HDL), apolipoprotein A-II (HDL), apolipoprotein C-I(VLDL), apolipoprotein C-II, apolipoprotein C-III (VLDL), apolipoproteinE, and the like. Among γ-mobility (non-immunoglobulin) examples include,but are not limited to, 0.6 S γ2-globulin, 2 S γ2-globulin, basicProtein B2, post-γ-globulin (γ-trace), and the like. Among low-molecularweight proteins examples include, but are not limited to, lysozyme,basic protein B1, basic protein B2, 0.6 S γ2-globulin, 2 S γ2-globulin,post γ-globulin, and the like.

Among complement components examples include, but are not limited to, C1esterase inhibitor, C1q component, C1r component, C1s component, C2component, C3 component, C3a component, C3b-inactivator, C4 bindingprotein, C4 component, C4a component, C4-binding protein, C5 component,C5a component, C6 component, C7 component, C8 component, C9 component,factor B, factor B (C3 proactivator), factor D, factor D (C3proactivator convertase), factor H, factor H (β₁H), properdin, and thelike. Among coagulation proteins examples include, but are not limitedto, antithrombin III, prothrombin, antihemophilic factor (factor VIII),plasminogen, fibrin-stabilizing factor (factor XIII), fibrinogen,thrombin, and the like.

Among cell-Related Plasma Proteins examples include, but are not limitedto, fibronectin, β-thromboglobulin, platelet factor-4, serum BasicProtease Inhibitor, and the like. Among amyloid proteins(Non-Immunoglobulin) examples include, but are not limited to,amyloid-Related apoprotein (apoSAA1), AA (FMF) (ASF), AA (TH) (AS),serum amyloid P component (9.5 S 7α1-glycoprotein), and the like. Amongmiscellaneous trace components examples include, but are not limited to,carcinoembryonic antigen, angiotensinogen, and the like.

In an embodiment, the sensor component 440 is configured to determine atleast one characteristic (e.g., a spectral characteristic, a spectralsignature, a physical quantity, a relative quantity, an environmentalattribute, a physiologic characteristic, or the like) associated with aregion within the biological subject. In an embodiment, the sensorcomponent 440 is configured to determine at least one characteristicassociated with a fluid-flow passageway 106 obstruction, a hematologicalabnormality, or a body fluid flow abnormality (e.g., a cerebrospinalfluid abnormality). In an embodiment, the sensor component 440 isconfigured to determine at least one characteristic associated with aportion of the tissue within the biological subject. In an embodiment,the sensor component 440 is configured to determine at least onecharacteristic associated with a biological fluid flow passageway.

In an embodiment, a controller 402 is configured to perform a comparisonof the at least one characteristic associated with the with thecerebrospinal fluid to stored reference data, and to initiate atreatment protocol based at least in part on the comparison. In anembodiment, a controller 402 is configured to perform a comparison ofthe at least one characteristic associated with the with thecerebrospinal fluid to stored reference data, and to cause at least oneof an emission of an energy stimulus from the one or more energyemitters to a cerebrospinal fluid received within at least one of theone or more fluid-flow passageways 106, and a delivery of an activeagent from at least one disinfecting agent reservoir to an interior ofat least one of the one or more fluid-flow passageways 106.

In an embodiment, the sensor component 440 is configured to determine atleast one characteristic associated with one or more biological markersor biological components (e.g., cerebrospinal fluid components). In anembodiment, the sensor component 440 is configured to determine at leastone characteristic associated with a tissue proximate the implantabledevice 102. In an embodiment, the sensor component 440 is configured todetermine a spatial dependence associated with the least onecharacteristic. In an embodiment, the sensor component 440 is configuredto determine a temporal dependence associated with the least onecharacteristic. In an embodiment, the sensor component 440 is configuredto concurrently or sequentially determine at least one spatialdependence associated with the least one characteristic and at least onetemporal dependence associated with the least one characteristic.

In an embodiment, the sensor component 440 is configured to determine atleast one spectral parameter associated with one or more imaging probes(e.g., chromophores, fluorescent agents, fluorescent marker,fluorophores, molecular imaging probes, quantum dots, radio-frequencyidentification transponders (RFIDs), x-ray contrast agents, or thelike). In an embodiment, the sensor component 440 is configured todetermine at least one characteristic associated with one or moreimaging probes attached, targeted to, conjugated, bound, or associatedwith at least one inflammation markers. See, e.g., the followingdocuments (the contents of which are incorporated herein by reference):Jaffer et al., Arterioscler. Thromb. Vasc. Biol. 2002; 22; 1929-1935(2002); Kalchenko et al., J. of Biomed. Opt. 11(5):50507 (2006).

In an embodiment, the one or more imaging probes include at least onecarbocyanine dye label. In an embodiment, the sensor component 440 isconfigured to determine at least one characteristic associated with oneor more imaging probes attached, targeted to, conjugated, bound, orassociated with at least one biomarker or biological fluid component.

In an embodiment, the one or more imaging probes include at least onefluorescent agent. In an embodiment, the one or more imaging probesinclude at least one quantum dot. In an embodiment, the one or moreimaging probes include at least one radio-frequency identificationtransponder. In an embodiment, the one or more imaging probes include atleast one x-ray contrast agent. In an embodiment, the one or moreimaging probes include at least one molecular imaging probe. Anon-limiting approach includes systems, devices, methods, andcompositions including, among other things, one or more imaging probes.

Among imaging probes examples include, but are not limited to,fluorescein (FITC), indocyanine green (ICG) and rhodamine B.Non-limiting examples of other fluorescent dyes for use in fluorescenceimaging include a number of red and near infrared emitting fluorophores(600-1200 nm) including cyanine dyes such as Cy5, Cy5.5, and Cy7(Amersham Biosciences, Piscataway, N.J., USA) or a variety of AlexaFluor dyes such as Alexa Fluor 633, Alexa Fluor 635, Alexa Fluor 647,Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750(Molecular Probes-Invitrogen, Carlsbad, Calif., USA; see, also, U.S.Patent Pub. No. 2005/0171434 (published Aug. 4, 2005) (the contents ofwhich are incorporated herein by reference), and the like.

Further non-limiting examples of imaging probes include IRDye800,IRDye700, and IRDye680 (LI-COR, Lincoln, Nebr., USA), NIR-1 and 1 C5-OSu(Dejindo, Kumamotot, Japan), LaJolla Blue (Diatron, Miami, Fla., USA),FAR-Blue, FAR-Green One, and FAR-Green Two (Innosense, Giacosa, Italy),ADS 790-NS, ADS 821-NS (American Dye Source, Montreal, CA), NIAD-4 (ICxTechnologies, Arlington, Va.), and the like. Further non-limitingexamples of fluorophores include BODIPY-FL, europium, green, yellow andred fluorescent proteins, luciferase, and the like. Quantum dots ofvarious emission/excitation properties can be used as imaging probes.See, e.g., Jaiswal, et al. Nature Biotech. 21:47-51 (2003) (the contentsof which are incorporated herein by reference). Further non-limitingexamples of imaging probes include those including antibodies specificfor leukocytes, anti-fibrin antibodies, monoclonal anti-diethylenetriamine pentaacetic acid (DTPA), DTPA labeled with Technetium-99m(^(99m)TC), and the like.

In an embodiment, the sensor component 440 is configured to detect atleast one of an emitted energy and a remitted energy associated with abiomarker. Among biomarker examples include, but are not limited to, oneor more substances that are measurable indicators of a biological stateand can be used as indicators of normal disease state, pathologicaldisease state, and/or risk of progressing to a pathological diseasestate. In some instances, a biomarker can be a normal blood componentthat is increased or decreased in the pathological state. A biomarkercan also be a substance that is not normally detected in biologicalsample, fluid, or tissue, but is released into circulation because ofthe pathological state. In some instances, a biomarker can be used topredict the risk, of developing a pathological state. For example,plasma measurement of lipoprotein-associated phospholipase A2 (Lp-PLA2)is approved by the U.S. Food & Drug Administration (FDA) for predictingthe risk of first time stroke. In other instances, the biomarker can beused to diagnose an acute pathological state. For example, elevatedplasma levels of S-100b, B-type neurotrophic growth factor (BNGF), vonWillebrand factor (vWF), matrix metalloproteinase-9 (MMP-9), andmonocyte chemoattractant protein-1 (MCP-1) are highly correlated withthe diagnosis of stroke (see, e.g., Reynolds, et al., Early biomarkersof stroke. Clin. Chem. 49:1733-1739 (2003), which is incorporated hereinby reference).

Further non-limiting examples of biomarkers include high-sensitivityC-reactive protein (hs-CRP), cardiac troponin T (cTnT), cardiac troponinI (cTnI), N-terminal-pro B-type natriuretic peptide (NT-proBNP),D-dimer, P-selectin, E-selectin, thrombin, interleukin-10, fibrinmonomers, phospholipid microparticles, creatine kinase, interleukin-6,tumor necrosis factor-alpha, myeloperoxidase, intracellular adhesionmolecule-1 (ICAM1), vascular adhesion molecule (VCAM), matrixmetalloproteinase-9 (MMP9), ischemia modified albumin (IMA), free fattyacids, choline, soluble CD40 ligand, insulin-like growth factor, (see,e.g., Giannitsis, et al. Risk stratification in pulmonary embolism basedon biomarkers and echocardiography. Circ. 112:1520-1521 (2005), Barnes,et al., Novel biomarkers associated with deep venous throbosis: Acomprehensive review. Biomarker Insights 2:93-100 (2007); Kamphuisen,Can anticoagulant treatment be tailored with biomarkers in patients withvenous thromboembolism? J. Throm. Haemost. 4:1206-1207 (2006); Rosalki,et al., Cardiac biomarkers for detection of myocardial infarction:Perspectives from past to present. Clin. Chem. 50:2205-2212 (2004);Apple, et al., Future biomarkers for detection of ischemia and riskstratification in acute coronary syndrome, Clin. Chem. 51:810-824(2005), which are incorporated herein by reference).

In an embodiment, the sensor component 440 is configured to detect atleast one characteristic associated with one or more biological fluidcomponents. In an embodiment, the at least one characteristic includesat least one of absorption coefficient information, extinctioncoefficient information, and scattering coefficient informationassociated with the at least one molecular probe. In an embodiment, theat least one characteristic includes spectral information indicative ofa rate of change, an accumulation rate, an aggregation rate, or a rateof change associated with at least one physical parameter associatedwith a biological fluid component.

In an embodiment, the sensor component 440 is configured to detect atleast characteristic associated with a biological subject. In anembodiment, the at least one characteristic includes at least one of atransmittance, an energy frequency change, a frequency shift, an energyphase change, and a phase shift. In an embodiment, the at least onecharacteristic includes at least one of a fluorescence, an intrinsicfluorescence, a tissue fluorescence, and a naturally occurringfluorophore fluorescence. In an embodiment, the at least onecharacteristic includes at least one of an electrical conductivity, andelectrical polarizability, and an electrical permittivity. In anembodiment, the at least one characteristic includes at least one of athermal conductivity, a thermal diffusivity, a tissue temperature, and aregional temperature.

In an embodiment, the at least one characteristic associated with abiological subject includes at least one parameter associated with adoppler optical coherence tomograph. (See, e.g., Li et al., Feasibilityof Interstitial Doppler Optical Coherence Tomography for In VivoDetection of Microvascular Changes During Photodynamic Therapy, Lasersin surgery and medicine 38(8):754-61. (2006), which is incorporatedherein by reference; see, also U.S. Pat. No. 7,365,859 (issued Apr. 29,2008), which is incorporated herein by reference).

In an embodiment, the at least one characteristic associated with abiological subject includes spectral signature information associatedwith an implant device. For example, in an embodiment, the at least onecharacteristic includes implant device spectral signature informationassociated with at least one of a bio-implants, bioactive implants,breast implants, cochlear implants, dental implants, neural implants,orthopedic implants, ocular implants, prostheses, implantable electronicdevice, implantable medical devices, and the like. Further non-limitingexamples of implant devices include replacements implants (e.g., jointreplacements implants such, for example, elbows, hip (an example ofwhich is shown on FIG. 1), knee, shoulder, wrists replacements implants,or the like), subcutaneous drug delivery devices (e.g., implantablepills, drug-eluting stents, or the like), shunts (e.g., cardiac shunts,lumbo-peritoneal shunts, cerebrospinal fluid shunts, cerebral shunts,pulmonary shunts, portosystemic shunts, portacaval shunts, or the like),stents (e.g., coronary stents, peripheral vascular stents, prostaticstents, ureteral stents, vascular stents, or the like), biological fluidflow controlling implants, and the like. Further non-limiting examplesof implant device include artificial hearts, artificial joints,artificial prosthetics, catheters, contact lens, mechanical heartvalves, subcutaneous sensors, urinary catheters, vascular catheters, andthe like.

In an embodiment, the at least one characteristic includes at least oneparameter associated with a diseased state. Inflammation is a complexbiological response to insults that can arise from, for example,chemical, traumatic, or infectious stimuli. It is a protective attemptby an organism to isolate and eradicate the injurious stimuli as well asto initiate the process of tissue repair. The events in the inflammatoryresponse are initiated by a complex series of interactions involvinginflammatory mediators, including those released by immune cells andother cells of the body. Histamines and eicosanoids such asprostaglandins and leukotrienes act on blood vessels at the site ofinfection to localize blood flow, concentrate plasma proteins, andincrease capillary permeability. Chemotactic factors, including certaineicosanoids, complement, and especially cytokines known as chemokines,attract particular leukocytes to the site of infection. Otherinflammatory mediators, including some released by the summonedleukocytes, function locally and systemically to promote theinflammatory response. Platelet activating factors and related mediatorsfunction in clotting, which aids in localization and can trap pathogens.Certain cytokines, interleukins and TNF, induce further trafficking andextravasation of immune cells, hematopoiesis, fever, and production ofacute phase proteins. Once signaled, some cells and/or their productsdirectly affect the offending pathogens, for example by inducingphagocytosis of bacteria or, as with interferon, providing antiviraleffects by shutting down protein synthesis in the host cells.

Oxygen radicals, cytotoxic factors, and growth factors can also bereleased to fight pathogen infection or to facilitate tissue healing.This cascade of biochemical events propagates and matures theinflammatory response, involving the local vascular system, the immunesystem, and various cells within the injured tissue. Under normalcircumstances, through a complex process of mediator-regulatedpro-inflammatory and anti-inflammatory signals, the inflammatoryresponse eventually resolves itself and subsides. For example, thetransient and localized swelling associated with a cut is an example ofan acute inflammatory response. However, in certain cases resolutiondoes not occur as expected. Prolonged inflammation, known as chronicinflammation, leads to a progressive shift in the type of cells presentat the site of inflammation and is characterized by simultaneousdestruction and healing of the tissue from the inflammatory process, asdirected by certain mediators. Rheumatoid arthritis is an example of adisease associated with persistent and chronic inflammation.

Non-limiting suitable techniques for optically measuring a diseasedstate may be found in, for example, U.S. Pat. No. 7,167,734 (issued Jan.23, 2007), which is incorporated herein by reference. In an embodiment,the at least one characteristic includes at least one of anelectromagnetic energy absorption parameter, an electromagnetic energyemission parameter, an electromagnetic energy scattering parameter, anelectromagnetic energy reflectance parameter, and an electromagneticenergy depolarization parameter. In an embodiment, the at least onecharacteristic includes at least one of an absorption coefficient, anextinction coefficient, and a scattering coefficient.

In an embodiment, the at least one characteristic associated with abiological subject includes at least one parameter associated with aninfection marker (e.g., an infectious agent marker), an inflammationmarker, an infective stress marker, a systemic inflammatory responsesyndrome marker, or a sepsis marker. Non-limiting examples of infectionmakers, inflammation markers, and the like may be found in, for example,Imam et al., Radiotracers for imaging of infection and inflammation—AReview, World J. Nucl. Med. 40-55 (2006), which is incorporated hereinby reference. Non-limiting characteristics associated with an infectionmarker, an inflammation marker, an infective stress marker, a systemicinflammatory response syndrome marker, or a sepsis marker include atleast one of an inflammation indication parameter, an infectionindication parameter, a diseased state indication parameter, and adiseased tissue indication parameter.

In an embodiment, the response includes generating a visual, an audio, ahaptic, or a tactile representation of at least one spectral parameterassociated with a detected infection marker. In an embodiment, theresponse includes generating a visual, an audio, a haptic, or a tactilerepresentation of at least one physical parameter indicative of at leastone dimension of infected tissue region.

In an embodiment, the at least one characteristic associated with abiological subject includes at least one of a tissue water content, anoxy-hemoglobin concentration, a deoxyhemoglobin concentration, anoxygenated hemoglobin absorption parameter, a deoxygenated hemoglobinabsorption parameter, a tissue light scattering parameter, a tissuelight absorption parameter, a hematological parameter, and a pH level.

In an embodiment, the at least one characteristic associated with abiological subject includes at least one hematological parameter.Non-limiting examples of hematological parameters include an albuminlevel, a blood urea level, a blood glucose level, a globulin level, ahemoglobin level, erythrocyte count, a leukocyte count, and the like. Inan embodiment, the infection marker includes at least one parameterassociated with a red blood cell count, a lymphocyte level, a leukocytecount, a myeloid count, an erythrocyte sedimentation rate, or aC-reactive protein level. In an embodiment, the at least onecharacteristic includes at least one parameter associated with acytokine plasma level or an acute phase protein plasma level. In anembodiment, the at least one characteristic includes at least oneparameter associated with a leukocyte level.

In an embodiment, a controller 402 is configured to compare a measurandassociated with the biological subject to a threshold value associatedwith a tissue spectral model and to generate a response based on thecomparison. In an embodiment, a controller 402 is configured to generatethe response based on the comparison of a measurand that modulates witha detected heart beat of the biological subject to a target valueassociated with a tissue spectral model. In an embodiment, a controller402 is configured to concurrently or sequentially operate multipleenergy emitters 302. In an embodiment, a controller 402 is configured tocompare an input associated with at least one characteristic associatedwith, for example, a tissue proximate an implantable device 102 to adatabase 422 of stored reference values, and to generate a responsebased in part on the comparison.

The response can include, but is not limited to, at least one of aresponse signal, an absorption parameter, an extinction parameter, ascattering parameter, a comparison code, a comparison plot, a diagnosticcode, a treatment code, an alarm response, and a test code based on thecomparison of a detected optical energy absorption profile tocharacteristic spectral signature information. In an embodiment, theresponse includes at least one of a display, a visual representation(e.g., a visual depiction representative of the detected (e.g.,assessed, calculated, evaluated, determined, gauged, measured,monitored, quantified, resolved, sensed, or the like) information)component, a visual display of at least one spectral parameter, and thelike. In an embodiment, the response includes a visual representationindicative of a parameter associated with an infection present in aregion of a tissue proximate one or more sensors 442. In an embodiment,the response includes a generating a representation (e.g., depiction,rendering, modeling, or the like) of at least one physical parameterassociated with a biological specimen.

Referring to FIG. 7, the implantable device 102 can include, but is notlimited to, one or more power sources 700. In an embodiment, the powersource 700 is electromagnetically, magnetically, ultrasonically,optically, inductively, electrically, or capacitively coupleable to atleast one of the energy emitters 302 and the sensor component 440. In anembodiment, the power source 700 is carried by the implantable device102. In an embodiment, the power source 700 comprises at least onerechargeable power source 702.

In an embodiment, the implantable device 102 includes one or morebiological-subject (e.g., human)-powered generators 704. In anembodiment, the biological-subject-powered generator 704 is configuredto harvest energy from for example, but not limited to, motion of one ormore joints. In an embodiment, the biological-subject-powered generator704 is configured to harvest energy generated by the biological subjectusing at least one of a thermoelectric generator 706, piezoelectricgenerator 708, electromechanical generator 710 (e.g., amicroelectromechanical systems (MEMS) generator, or the like),biomechanical-energy harvesting generator 712, and the like.

In an embodiment, the biological-subject-powered generator 704 isconfigured to harvest thermal energy generated by the biologicalsubject. In an embodiment, a thermoelectric generator 706 is configuredto harvest heat dissipated by the biological subject. In an embodiment,the biological-subject-powered generator 704 is configured to harvestenergy generated by any physical motion or movement (e.g., walking,) bybiological subject. For example, in an embodiment, thebiological-subject-powered generator 704 is configured to harvest energygenerated by the movement of a joint within the biological subject. Inan embodiment, the biological-subject-powered generator 704 isconfigured to harvest energy generated by the movement of a fluid (e.g.,biological fluid) within the biological subject.

Among power sources 700 examples include, but are not limited to, one ormore button cells, chemical battery cells, a fuel cell, secondary cells,lithium ion cells, micro-electric patches, nickel metal hydride cells,silver-zinc cells, capacitors, super-capacitors, thin film secondarycells, ultra-capacitors, zinc-air cells, and the like. Furthernon-limiting examples of power sources 700 include one or moregenerators (e.g., electrical generators, thermo energy-to-electricalenergy generators, mechanical-energy-to-electrical energy generators,micro-generators, nano-generators, or the like) such as, for example,thermoelectric generators, piezoelectric generators, electromechanicalgenerators, biomechanical-energy harvesting generators, and the like. Inan embodiment, the implantable device 102 includes one or moregenerators configured to harvest mechanical energy from for example,ultrasonic waves, mechanical vibration, blood flow, and the like. In anembodiment, the implantable device 102 includes one or more powerreceivers 732 configured to receive power from an in vivo or ex vivopower source.

In an embodiment, the power source 700 includes at least one of athermoelectric generator, a piezoelectric generator, anelectromechanical generator, and a biomechanical-energy harvestinggenerator, and at least one of a button cell, a chemical battery cell, afuel cell, a secondary cell, a lithium ion cell, a micro-electric patch,a nickel metal hydride cell, silver-zinc cell, a capacitor, asuper-capacitor, a thin film secondary cell, an ultra-capacitor, and azinc-air cell. In an embodiment, the power source 700 includes at leastone rechargeable power source.

In an embodiment, the implantable device 102 includes a power source 700including at least one of a thermoelectric generator a piezoelectricgenerator, an electromechanical generator, and a biomechanical-energyharvesting generator. In an embodiment, the power source is configuredto manage a duty cycle associated with emitting an effective amount ofthe energy stimulus from the one or more energy emitters 302. In anembodiment, the power source 700 is configured to manage a duty cycleassociated with emitting an effective amount of a sterilizing energystimulus from the one or more energy emitters 302. In an embodiment, theone or more energy emitters 302 are configured to provide a voltageacross at least a portion of the tissue proximate the implantable device102 from a power source 700 coupled to the implantable device 102.

The implantable device 102 can include a transcutaneous energy transfersystem 714. In an embodiment, the transcutaneous energy transfer system714 is configured to transfer power from an in vivo power source to theimplantable device 102. In an embodiment, the transcutaneous energytransfer system 714 is configured to transfer power to the implantabledevice 102 and to recharge a power source 700 within the implantabledevice 102. In an embodiment, the implantable device 102 can include,but is not limited to, at least one of a battery, a capacitor, and amechanical energy store (e.g., a spring, a flywheel, or the like).

In an embodiment, the transcutaneous energy transfer system 714 iselectromagnetically, magnetically, ultrasonically, optically,inductively, electrically, or capacitively coupleable to an in vivopower supply. In an embodiment, the transcutaneous energy transfersystem 714 is electromagnetically, magnetically, ultrasonically,optically, inductively, electrically, or capacitively coupleable to theenergy emitter component 304. In an embodiment, the transcutaneousenergy transfer system 714 includes at least one electromagneticallycoupleable power supply 716, magnetically coupleable power supply 718,ultrasonically coupleable power supply 720, optically coupleable powersupply 722, inductively coupleable power supply 724, electricallycoupleable power supply 726, or capacitively coupleable power supply728. In an embodiment, the energy transcutaneous transfer system 714 isconfigured to wirelessly receive power from a remote power supply 730.

The transcutaneous energy transfer system 714 can include, but is notlimited to, an inductive power supply. In an embodiment, the inductivepower supply includes a primary winding operable to produce a varyingmagnetic field. The implantable device 102 can include, but is notlimited to, a secondary winding electrically coupled to one or moreenergy emitters 302 for providing a voltage to tissue proximate theimplantable device 102 in response to the varying magnetic field of theinductive power supply. In an embodiment, the transcutaneous energytransfer system 714 includes a secondary coil configured to provide anoutput voltage ranging from about 10 volts to about 25 volts. In anembodiment, the transcutaneous energy transfer system 714 is configuredto manage a duty cycle associated with emitting an effective amount ofthe sterilizing energy stimulus from one or more energy emitters 302. Inan embodiment, the transcutaneous energy transfer system 714 isconfigured to transfer power to the implantable device 102 and torecharge a power source 700 within the implantable device 102. In anembodiment, the power source 700 is configured to wirelessly receivepower from a remote power supply 730. In an embodiment, the in vivopower source includes at least one of a thermoelectric generator, apiezoelectric generator, a microelectromechanical systems generator, anda biomechanical-energy harvesting generator.

FIG. 8 shows a system 100 in which one or more methodologies ortechnologies can be implemented such as, for example, managing atransport of biological fluids and actively detecting, treating, orpreventing an infection (e.g., an implant-associated infection, ahematogenous implant-associated infection, or the like), a biologicalfluid abnormality, or the like. A non-limiting approach for treating orpreventing an infection, biological fluid abnormality, or the likeincludes systems, devices, and methods for administrating aperioperative antibiotic prophylaxis to a patient. Another non-limitingapproach includes systems, devices, methods, and compositions foractively forming an antimicrobial agent, in vivo. Another non-limitingapproach includes systems, devices, methods, and compositions forimpeding bacterial adherence to the implantable device 102 surfaces.Another non-limiting approach includes systems, devices, methods, andcompositions for actively impeding biofilm formation on the implantabledevice 102. Another non-limiting approach includes systems, devices, andmethods including coating the implantable device 102 with active agentcompositions having, for example, anti-biofilm activity. Anothernon-limiting approach includes systems, devices, and methods includingcoating the implantable device 102 with one or more coatings havingself-cleaning properties. Another non-limiting approach includessystems, devices, and methods including an implant with a self-cleaningcoating having self-cleaning, and anti-bacterial activity. Anothernon-limiting approach includes systems, devices, and methods includingan implantable device 102 having one or more self-cleaning surfaces. Yetanother non-limiting approach includes systems, devices, and methodsconfigured to treat or reduce the concentration of an infectious agentin the immediate vicinity of the implantable device 102.

In an embodiment, at least a portion of an inner or an outer surface ofthe implantable device 102 includes one or more coatings, functionalizedsurfaces, surface treatments, immuno-stimulating coatings, and the like.In an embodiment, at least a portion of one or more of the fluid-flowpassageways 106 includes one or more coatings, functionalized surfaces,surface treatments, immuno-stimulating coatings, and the like. In anembodiment, at least a portion of the body structure 104 includes one ormore coatings, functionalized surfaces, surface treatments,immuno-stimulating coatings, and the like.

Among the one or more coatings, functionalized surfaces, surfacetreatments, immuno-stimulating coatings, and the like, examples include,but are not limited to, polymeric compositions that resist bacterialadhesion, antimicrobial coating, coatings that controllably releaseantimicrobial agents, quaternary ammonium silane coatings, chitosancoatings, and the like. Further non-limiting examples of coatings,functionalized surfaces, surface treatments, immuno-stimulatingcoatings, and the like may be found in, for example, the followingdocuments (the contents of which are incorporated herein by reference):U.S. Pat. Nos. 7,348,021 (issued Mar. 25, 2008), 7,217,425 (issued May15, 2007), 7,151,139 (issued Dec. 19, 2006), and 7,143,709 (issued Dec.5, 2006). In an embodiment, at least a portion of an inner or an outersurface of the implantable device 102 includes one or more self-cleaningcoating materials. Examples of self-cleaning coating (e.g., LotusEffect) materials include, but are not limited to titanium dioxide,superhydrophobic materials, carbon nanotubes with nanoscopic paraffincoating, or the like. Further non-limiting examples of self-cleaning(e.g., non fouling) coating materials include antimicrobial, andnonfouling zwitterionic polymers, zwitterionic surface formingmaterials, zwitterionic polymers, poly(carboxybetaine methacrylate)(pCBMA), poly(carboxybetaine acrylic amide) (pCBAA), poly(oligo(ethyleneglycol) methyl ether methacrylate) (pOEGMA),poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2′-(methacryloyloxy)ethyl]-ammoniumbromide), cationic pC8NMA, switchable pCBMA-1 C2, pCBMA-2, and the like.See, e.g., WO 2008/083390 (published Jul. 10, 2008) (the contents ofwhich are incorporated herein by reference).

Further non-limiting examples of coatings include superhydrophobicconducting polypyrrole films, coating, or components that areelectrically switchable between an oxidized state and a neutral state,resulting in reversibly switchable superhydrophobic and superhydrophilicproperties (see, e.g., Lahann et al., A Reversibly Switching Surface,299 (5605): 371-374 (2003) 21:47-51 (2003), the contents of which areincorporated herein by reference); coatings including electricallyisolatable fluid-support structures (see, e.g., U.S. Pat. No. 7,535,692(issued May 19, 2009), the contents of which are incorporated herein byreference); coatings including a plurality of volume-tunablenanostructures (see, e.g., U.S. Patent Publication No. 2008/0095977(published Apr. 24, 2008), the contents of which are incorporated hereinby reference); coatings including re-entrant surface structures (see,e.g., Tuteja et al., Robust Omniphobic Surfaces, Epub 2008 Nov. 10,105(47):18200-5 (2008), the contents of which are incorporated herein byreference); coatings including superhydrophobic conducting polypyrrolematerials, coatings including zwitterionic polymers (see, e.g., Cheng etal., A Switchable Biocompatible Polymer Surface with Self-Sterilizingand Nonfouling Capabilities, Agnew. Chem. Int. Ed. 8831-8834 (2008), thecontents of which are incorporated herein by reference); or the like.

In an embodiment, the implantable device 102 includes at least oneactive agent assembly 800 including one or more reservoirs 802. In anembodiment, the implantable device 102 includes one or more active agentassemblies 800 configured to deliver at least one active agent from theat least one reservoir 802 to at least one of a region 804 proximate anouter surface 108 and a region 806 proximate an inner surface 110 of theimplantable device 102. In an embodiment, the implantable device 102includes one or more active agent reservoirs 802 including at least oneactive agent composition. Among active agents, examples include, but arenot limited to, adjuvants, allergens, analgesics, anesthetics,antibacterial agents, antibiotics, antifungals, anti-inflammatory agents(e.g., nonsteroidal anti-inflammatory drugs), antimicrobials,antioxidants, antipyretics, anti-tumor agents, antivirals, bio-controlagents, biologics or bio-therapeutics, chemotherapy agents, disinfectingagents, energy-activatable active agents, immunogens, immunologicaladjuvants, immunological agents, immuno-modulators, immuno-responseagents, immuno-stimulators (e.g., specific immuno-stimulators,non-specific immuno-stimulators, or the like), immuno-suppressants,non-pharmaceuticals (e.g., cosmetic substances, or the like),pharmaceuticals, protease inhibitors or enzyme inhibitors, receptoragonists, receptor antagonists, therapeutic agents, tolerogens,toll-like receptor agonists, toll-like receptor antagonists, vaccines,or combinations thereof.

Further non-limiting examples of active agents include nonsteroidalanti-inflammatory drugs such as acemetacin, aclofenac, aloxiprin,amtolmetin, aproxen, aspirin, azapropazone, benorilate, benoxaprofen,benzydamine hydrochloride, benzydamine hydrochloride, bromfenal,bufexamac, butibufen, carprofen, celecoxib, choline salicylate,clonixin, desoxysulindac, diflunisal, dipyone, droxicam, etodolac,etofenamate, etoricoxib, felbinac, fenbufen, fenoprofen, fentiazac,fepradinol, floctafenine, flufenamic acid, indomethacin, indoprofen,isoxicam, ketoralac, licofelone, lomoxicam, loxoprofen, magnesiumsalicylate, meclofenamic acid, meclofenamic acid, mefenamic acid,meloxicam, morniflumate, niflumic acid, nimesulide, oxaprozen,phenylbutazone, piketoprofen, piroxicam, pirprofen, priazolac,propyphenazone, proquazone, rofecoxib, salalate, salicylamide, salicylicacid, sodium salicylate, sodium thiosalicylate, sulindac, suprofen,tenidap, tenoxicam, tiaprofenic acid, tolmetin, tramadol, trolaminesalicylate, zomepirac, or the like. Further non-limiting examples ofactive agents include energy (e.g., chemical energy, electricalresistance, laser energy, terahertz energy, microwave energy, opticalenergy, radio frequency energy, sonic energy, thermal energy, thermalresistance heating energy or ultrasonic energy, or the like)-activatableactive agents, and the like.

In an embodiment, the active agent includes at least one active agentthat selectively targets bacteria. For example, in an embodiment, theactive agent includes at least one bacteriophage that can, for example,selectively target bacteria. Bacteriophages generally comprise an outerprotein hull enclosing genetic material. The genetic material can bessRNA, dsRNA, ssDNA, or dsDNA. Bacteriophages are generally smaller thanthe bacteria they destroy generally ranging from about 20 nm to about200 nm. Non-limiting examples of bacteriophages include T2, T4, T6,phiX-174, MS2, or the like). In an embodiment, the active agent includesat least one energy-activatable agent that selectively targets bacteria.For example, in an embodiment, the active agent includes at least onetriplet excited-state photosensitizer that can, for example, selectivelytarget bacteria.

Further non-limiting examples of active agents include tripletexcited-state photosensitizers, reactive oxygen species, reactivenitrogen species, any other inorganic or organic ion or molecules thatinclude oxygen ions, free radicals, peroxides, or the like. Furthernon-limiting examples of active agents include compounds, molecules, ortreatments that elicit a biological response from any biologicalsubject. Further non-limiting examples of disinfecting agents include,therapeutic agents (e.g., antimicrobial therapeutic agents),pharmaceuticals (e.g., a drug, a therapeutic compound, pharmaceuticalsalts, or the like) non-pharmaceuticals (e.g., a cosmetic substance, orthe like), neutraceuticals, antioxidants, phytochemicals, homeopathicagents, and the like. Further non-limiting examples of disinfectingagents include peroxidases (e.g., haloperoxidases such aschloroperoxidase, or the like), oxidoreductase (e.g., myeloperoxidase,eosinophil peroxidase, lactoperoxidase, or the like) oxidases, and thelike.

Further non-limiting examples of active agents include one or morepore-forming toxins. Non limiting examples of pore-forming toxinsinclude beta-pore-forming toxins, e.g., hemolysin, Panton-Valentineleukocidin S, aerolysin, Clostridial epsilon-toxin; binary toxins, e.g.,anthrax, C. perfringens iota toxin, C. difficile cytolethal toxins;cholesterol-dependent cytolysins; pneumolysin; small pore-formingtoxins; and gramicidin A.

Further non-limiting examples of active agents include one or morepore-forming antimicrobial peptides. Antimicrobial peptides represent anabundant and diverse group of molecules that are naturally produced bymany tissues and cell types in a variety of invertebrate, plant andanimal species. The amino acid composition, amphipathicity, cationiccharge and size of antimicrobial peptides allow them to attach to andinsert into microbial membrane bilayers to form pores leading tocellular disruption and death. More than 800 different antimicrobialpeptides have been identified or predicted from nucleic acid sequences,a subset of which are available in a public database (see, e.g., Wang &Wang, Nucleic Acids Res. 32:D590-D592, 2004);http://aps.unmc.edu/AP/main.php, which is incorporated herein byreference). More specific examples of antimicrobial peptides include,but are not limited to, anionic peptides, e.g., maximin H5 fromamphibians, small anionic peptides rich in glutamic and aspartic acidsfrom sheep, cattle and humans, and dermcidin from humans; linearcationic alpha-helical peptides, e.g., cecropins (A), andropin, moricin,ceratotoxin, and melittin from insects, cecropin P1 from Ascarisnematodes, magainin 2, dermaseptin, bombinin, brevinin-1, esculentinsand buforin II from amphibians, pleurocidin from skin mucous secretionsof the winter flounder, seminalplasmin, BMAP, SMAP (SMAP29, ovispirin),PMAP from cattle, sheep and pigs, CAP18 from rabbits and LL37 fromhumans; cationic peptides enriched for specific amino acids, e.g.,praline-containing peptides including abaecin from honeybees, praline-and arginine-containing peptides including apidaecins from honeybees,drosocin from Drosophila, pyrrhocoricin from European sap-sucking bug,bactenicins from cattle (Bac7), sheep and goats and PR-39 from pigs,praline- and phenylalanine-containing peptides including prophenin frompigs, glycine-containing peptides including hymenoptaecin fromhoneybees, glycine- and praline-containing peptides includingcoleoptericin and holotricin from beetles, tryptophan-containingpeptides including indolicidin from cattle, and small histidine-richsalivary polypeptides, including histatins from humans and higherprimates; anionic and cationic peptides that contain cysteine and fromdisulfide bonds, e.g., peptides with one disulphide bond includingbrevinins, peptides with two disulfide bonds including alpha-defensinsfrom humans (HNP-1, HNP-2, cryptidins), rabbits (NP-1) and rats,beta-defensins from humans (HBD1, DEFB118), cattle, mice, rats, pigs,goats and poultry, and rhesus theta-defensin (RTD-1) from rhesus monkey,insect defensins (defensin A); and anionic and cationic peptidefragments of larger proteins, e.g., lactoferricin from lactoferrin,casocidin 1 from human casein, and antimicrobial domains from bovinealpha-lactalbumin, human hemoglobin, lysozyme, and ovalbumin (see, e.g.,Brogden, Nat. Rev. Microbiol. 3:238-250, 2005, which is incorporatedherein by reference).

Further non-limiting examples of active agents include antibacterialdrugs. Non-limiting examples of antibacterial drugs include beta-lactamcompounds such as penicillin, methicillin, nafcillin, oxacillin,cloxacillin, dicloxacillin, ampicillin, ticarcillin, amoxicillin,carbenicillin, and piperacillin; cephalosporins and cephamycins such ascefadroxil, cefazolin, cephalexin, cephalothin, cephapirin, cephradine,cefaclor, cefamandole, cefonicid, cefuroxime, cefprozil, loracarbef,ceforanide, cefoxitin, cefmetazole, cefotetan, cefoperazone, cefotaxime,ceftazidine, ceftizoxine, ceftriaxone, cefixime, cefpodoxime, proxetil,cefdinir, cefditoren, pivoxil, ceftibuten, moxalactam, and cefepime;other beta-lactam drugs such as aztreonam, clavulanic acid, sulbactam,tazobactam, ertapenem, imipenem, and meropenem; other cell wall membraneactive agents such as vancomycin, teicoplanin, daptomycin, fosfomycin,bacitracin, and cycloserine; tetracyclines such as tetracycline,chlortetracycline, oxytetracycline, demeclocycline, methacycline,doxycycline, minocycline, and tigecycline; macrolides such aserythromycin, clarithromycin, azithromycin, and telithromycin;aminoglycosides such as streptomycin, neomycin, kanamycin, amikacin,gentamicin, tobramycin, sisomicin, and netilmicin; sulfonamides such assulfacytine, sulfisoxazole, silfamethizole, sulfadiazine,sulfamethoxazole, sulfapyridine, and sulfadoxine; fluoroquinolones suchas ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin,lomefloxacin, moxifloxacin, norfloxacin, and ofloxacin; antimycobacteriadrugs such as isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide,ethambutol, ethionamide, capreomycin, clofazimine, and dapsone; andmiscellaneous antimicrobials such as colistimethate sodium, methenaminehippurate, methenamine mandelate, metronidazole, mupirocin,nitrofurantoin, polymyxin B, clindamycin, choramphenicol,quinupristin-dalfopristin, linezolid, spectrinomycin, trimethoprim,pyrimethamine, and trimethoprim-sulfamethoxazole.

Further non-limiting examples of active agents include antifungalagents. Non-limiting examples of antifungal agents includeanidulafungin, amphotericin B, butaconazole, butenafine, caspofungin,clotrimazole, econazole, fluconazole, flucytosine griseofulvin,itraconazole, ketoconazole, miconazole, micafungin, naftifine,natamycin, nystatin, oxiconazole, sulconazole, terbinafine, terconazole,tioconazole, tolnaftate, and/or voriconazole.

Further non-limiting examples of active agents include anti-parasiteagents. Non-limiting examples of anti-parasite agents includeantimalaria drugs such as chloroquine, amodiaquine, quinine, quinidine,mefloquine, primaquine, sulfadoxine-pyrimethamine, atovaquone-proguanil,chlorproguanil-dapsone, proguanil, doxycycline, halofantrine,lumefantrine, and artemisinins; treatments for amebiasis such asmetronidazole, iodoquinol, paromomycin, diloxanide furoate, pentamidine,sodium stibogluconate, emetine, and dehydroemetine; and otheranti-parasite agents such as pentamidine, nitazoxanide, suramin,melarsoprol, eflomithine, nifurtimox, clindamycin, albendazole, andtimidazole. Further non-limiting examples of active agents include ionicsilver, (SilvaSorb®, Medline Industries, Inc), anti-microbial silvercompositions (Arglaes®, Medline Industries, Inc), or the like. Furthernon-limiting examples of active agents include superoxide-formingcompositions. Further non-limiting examples of active agents includeoxazolidinones, gram-positive antibacterial agents, or the like. See,e.g., U.S. Pat. No. 7,322,965 (issued Jan. 29, 2008), which isincorporated herein by reference.

In an embodiment, the active agent includes one or more antimicrobialagents. In an embodiment, the antimicrobial agent is an antimicrobialpeptide. Amino acid sequence information for a subset of these can befound as part of a public database (see, e.g., Wang & Wang, NucleicAcids Res. 32:D590-D592, 2004); http://aps.unmc.edu/AP/main.php, whichis incorporated herein by reference). Alternatively, a phage library ofrandom peptides can be used to screen for peptides with antimicrobialproperties against live bacteria, fungi and/or parasites. The DNAsequence corresponding to an antimicrobial peptide can be generated exvivo using standard recombinant DNA and protein purification techniques.

In an embodiment, one or more of the active agent include chemicalssuitable to disrupt or destroy cell membranes. For example, someoxidizing chemicals can withdraw electrons from a cell membrane causingit to, for example, become destabilized. Destroying the integrity ofcell membranes of, for example, a pathogen can lead to cell death.

In an embodiment, the implantable device 102 includes one or more activeagent assemblies 800 configured to deliver at least one active agentfrom the at least one reservoir 802 to at least one of a regionproximate an outer and an inner surface of the implantable device 102.In an embodiment, at least one of the one or more active agentassemblies 800 is configured to deliver one or more active agents in aspatially patterned distribution. In an embodiment, at least one of theone or more active agent assemblies 800 is configured to deliver one ormore active agents in a temporally patterned distribution. In anembodiment, the implantable device 102 includes a plurality of spacedapart release ports 808 adapted to deliver one or more active agents ina spatially patterned distribution. In an embodiment, the implantabledevice 102 includes a plurality of spaced apart controllable-releaseports 808 adapted to deliver one or more active agents in a spatiallypatterned distribution. In an embodiment, a controller 402 is operablycoupled to the active agent assembly 800 and configured to control atleast one of an active agent delivery rate, an active agent deliveryamount, a active agent delivery composition, a port release rate, a portrelease amount, and a port release pattern. In an embodiment, thecontroller 402 is operably coupled to the active agent assembly andconfigured to actively control one or more of the plurality of spacedapart release ports. In an embodiment, at least one controller 402 isoperably coupled to one or more of the spaced-apart controllable-releaseports 808 and configured to control at least one of a port release rate,a port release amount, and a port release pattern associated with adelivery of the one or more active agents. In an embodiment, at leastone processor 404 is operably coupled to the active agent assembly 800and configured to control at least one of a port release rate, a portrelease amount, and a port release pattern associated with the deliveryof the one or more active agents from the at least one active agentreservoir 810 to an interior of at least one of the one or morefluid-flow passageways 106.

In an embodiment, at least one controller 402 is operably coupled to oneor more of the plurality of spaced apart release ports 808 andconfigured to actuate one or more of the plurality of spaced apartrelease ports 808 between an active agent discharge state and an activeagent retention state. In an embodiment, the implantable device 102includes one or more active agent assemblies 800 including one or moreactive agent reservoirs 810 configured to deliver at least one activeagent from the at least one active agent reservoirs 810 to at least oneof a region 804 proximate an outer surface 108 and a region 806proximate an inner surface 110 of the implantable device 102.

In an embodiment, the active agent assembly 800 comprises a disinfectingagent assembly including at least one disinfecting agent reservoir 812.In an embodiment, the disinfecting agent assembly is configured todeliver one or more disinfecting agents from the at least onedisinfecting agent reservoir 812 to an interior of at least one of theone or more fluid-flow passageways 106. In an embodiment, the activeagent assembly 800 comprises an energy-activatable agent assemblyincluding at least one energy-activatable agent reservoir 814. In anembodiment, the energy-activatable agent assembly is configured todeliver one or more energy-activatable agents from the at least oneenergy-activatable agent reservoir 814 to an interior of at least one ofthe one or more fluid-flow passageways 106.

In an embodiment, the implantable device 102 includes one or more activeagent assemblies 800 configured to deliver at least oneenergy-activatable agent from at least one reservoir 802 to, forexample, an interior of one or more fluid-flow passageways 106.Non-limiting examples of energy-activatable active agents includeradiation absorbers, light energy absorbers, X-ray absorbers,photoactive agents, and the like. Non-limiting examples of photoactiveagents include, but are not limited to photoactive antimicrobial agents(e.g., eudistomin, photoactive porphyrins, photoactive TiO₂,antibiotics, silver ions, antibodies, nitric oxide, or the like),photoactive antibacterial agents, photoactive antifungal agents, and thelike. Further non-limiting examples of energy-activatable agent includesenergy-activatable disinfecting agents, photoactive agents, or ametabolic precursor thereof. In an embodiment, the at least oneenergy-activatable agent includes at least one X-ray absorber. In anembodiment, the at least one energy-activatable agent includes at leastone radiation absorber.

In an embodiment, the active agent assembly 800 is configured to deliverat least one energy-activatable disinfecting agent from at least onereservoir 802 to a biological fluid 808 received within one or morefluid-flow passageways 106. In an embodiment, the implantable device 102includes one or more active agent assemblies 800 configured to deliverat least one energy-activatable disinfecting agent from the at least oneactive agent reservoir to tissue 810 proximate at least one surface ofthe implantable device 102. In an embodiment, at least one of the one ormore active agent assemblies 800 is configured to deliver at least oneenergy-activatable disinfecting agent in a spatially patterneddistribution. In an embodiment, the active agent assembly 800 isconfigured to deliver at least one energy-activatable steroid to tissueproximate the at least one outer surface 108 of the implantable device102.

The at least one active agent reservoir 802 can include, for example,but not limited to an acceptable carrier. In an embodiment, at least oneactive agent is carried by, encapsulated in, or forms part of, anenergy-sensitive (e.g., energy-activatable), carrier, vehicle, vesicle,pharmaceutical vehicle, pharmaceutical carrier, pharmaceuticallyacceptable vehicle, pharmaceutically acceptable carrier, or the like.

Non-limiting examples of carriers include any matrix that allows fortransport of, for example, a disinfecting agent across any tissue, cellmembranes, and the like of a biological subject, or that is suitable foruse in contacting a biological subject, or that allows for controlledrelease formulations of the compositions disclosed herein. Furthernon-limiting examples of carriers include at least one of creams,liquids, lotions, emulsions, diluents, fluid ointment bases, gels,organic and inorganic solvents, degradable or non-degradable polymers,pastes, salves, vesicle, and the like. Further non-limiting examples ofcarriers include cyclic oligosaccharides, ethasomes, hydrogels,liposomes, micelle, microspheres, nisomes, non-ionic surfactantvesicles, organogels, phospholipid surfactant vesicles, phospholipidsurfactant vesicles, transfersomes, virosomes. Further non-limitingexamples of energy-sensitive carriers and the like include electricalenergy-sensitive, light sensitive, pH-sensitive, ion-sensitive, sonicenergy sensitive, ultrasonic energy sensitive carriers.

In an embodiment, one or more active agents are carried byenergy-sensitive vesicles (e.g., energy-sensitive cyclicoligosaccharides, ethasomes, hydrogels, liposomes, micelles,microspheres, nisomes, non-ionic surfactant vesicles, organogels,phospholipid surfactant vesicles, transfersomes, virosomes, and thelike). In an embodiment, at least one of the one or more energy emitters302 is configured to provide energy of a character and for a timesufficient to liberate at least a portion of an active agent carried bythe energy-sensitive vesicles.

In an embodiment, the implantable device 102 includes one or morebiological fluid reservoirs. In an embodiment, the implantable device102 includes one or more biological specimen reservoirs. In anembodiment, the implantable device 102 includes one or morecerebrospinal fluid reservoirs. In an embodiment, the implantable device102 includes one or more active agent assemblies 800 configured toreceive one or more biological fluids. In an embodiment, the biologicalfluid reservoir is placed under the scalp of a user. In an embodiment,the biological fluid reservoir is configured to allow for the removal ofcerebrospinal fluid with a syringe. In an embodiment, the reservoir isconfigured to detect bacteria, cancer cells, blood, or proteins of afluid sample received within. In an embodiment, the biological fluidreservoir is configured to allow the injection or introduction ofantibiotics for cerebrospinal fluid infection or chemotherapymedication. In an embodiment, the reservoir includes circuitryconfigured to detect at least one physical quantity, environmentalattribute, or physiologic characteristic associated with, for example, ashunting process.

In an embodiment, the one or more active agent assemblies 800 areconfigured to deliver one or more tracer agents. In an embodiment, theimplantable device 102 includes one or more active agent assemblies 800configured to deliver at least one tracer agent from at least onereservoir 802. In an embodiment, the implantable device 102 includes oneor more active agent assemblies 800 including one or more tracer agentreservoirs 810 configured to deliver at least one tracer agent. In anembodiment, active agent assembly 800 is further configured toconcurrently or sequentially deliver one or more tracer agents and oneor more energy-activatable disinfecting agents. In an embodiment, theactive agent assembly 800 is further configured to deliver one or moretracer agents for indicating the presence or concentration of one ormore energy-activatable disinfecting agents in at least a regionproximate the implantable device 102. In an embodiment, the active agentassembly 800 is further configured to deliver one or more tracer agentsfor indicating the response of the one or more energy-activatabledisinfecting agents to energy emitted from the one or moreenergy-emitting emitters 302.

Among tracer agents, examples include one or more in vivo clearanceagents, magnetic resonance imaging agents, contrast agents, dye-peptidecompositions, fluorescent dyes, or tissue specific imaging agents. In anembodiment, the one or more tracer agents include at least onefluorescent dye. In an embodiment, the one or more tracer agents includeindocyanine green.

In an embodiment, at least one of the one or more fluid-flow passageways106 includes a photoactive agent. In an embodiment, at least one of theone or more fluid-flow passageways 106 includes a photoactive coatingmaterial. In an embodiment, at least one of the one or more fluid-flowpassageways 106 includes a photoactive agent configured to emitultraviolet light energy in the presence of an energy stimulus. In anembodiment, at least one of the one or more fluid-flow passageways 106includes a photoactive agent configured to emit ultraviolet light energyin the presence of an electrical potential. In an embodiment, at leastone of the one or more fluid-flow passageways 106 includes a photoactiveagent having one or more photoabsorption bands in the visible region ofthe electromagnetic spectrum.

Referring to FIG. 9, in an embodiment, the system 100 includes at leastone energy-emitting component 902. Among energy-emitting components 902examples include, but are not limited to, electric circuits, electricalconductors, electrodes (e.g., nano- and micro-electrodes,patterned-electrodes, electrode arrays (e.g., multi-electrode arrays,micro-fabricated multi-electrode arrays, patterned-electrode arrays, orthe like), electrocautery electrodes, or the like), cavity resonators,conducting traces, ceramic patterned electrodes, electro-mechanicalcomponents, lasers, quantum dots, laser diodes, light-emitting diodes(e.g., organic light-emitting diodes, polymer light-emitting diodes,polymer phosphorescent light-emitting diodes, microcavity light-emittingdiodes, high-efficiency UV light-emitting diodes, or the like), arcflashlamps, incandescent emitters, transducers, heat sources, continuouswave bulbs, a quantum dot, ultrasound emitting elements, ultrasonictransducers, thermal energy emitting elements, and the like.

In an embodiment, the at least one energy-emitting component 902 isconfigured to provide an energy stimulus. In an embodiment, theenergy-emitting component 902 includes a patterned-energy emittingsource 338. In an embodiment, the energy-emitting component 902 includesone or more energy emitters 302.

In an embodiment, the at least one energy-emitting component 902includes a plurality of electrodes 330, the plurality of electrodes 330configured to provide a spatially patterned sterilizing energy stimulus.In an embodiment, the at least one energy-emitting component 902includes a plurality of light emitting diodes 310 configured to providea spatially patterned sterilizing energy stimulus. In an embodiment, theat least one energy-emitting component 902 is configured to provide anillumination pattern comprising at least a first region and a secondregion, the second region having at least one of an illuminationintensity, an energy-emitting pattern, a peak emission wavelength, anON-pulse duration, an OFF-pulse duration, and a pulse frequencydifferent from the first region. In an embodiment, the at least oneenergy-emitting component 902 is configured to deliver electromagneticradiation of a character and for a time sufficient to induce PCD withoutsubstantially inducing necrosis of a tissue proximate the outer portionof the one or more fluid-flow passageways 106. In an embodiment, the atleast one energy-emitting component 902 is configured to deliver asufficient amount of an ultraviolet radiation to induce cell death byPCD. In an embodiment, the at least one energy-emitting component 902 isconfigured to deliver an effective dose of optical energy at which acell preferentially undergoes PCD compared to necrosis. In anembodiment, the at least one energy-emitting component 902 is configuredto deliver a sufficient amount of an optical energy to initiateultraviolet energy induced PCD. In an embodiment, the at least oneenergy-emitting component 902 includes at least one ultraviolet energyemitter. In an embodiment, the at least one energy-emitting component902 includes at least one ultraviolet B energy emitter. In anembodiment, the at least one energy-emitting component 902 includes atleast one ultraviolet C energy emitter. In an embodiment, the at leastone energy-emitting component 902 comprises a peak emission wavelengthranging from about 100 nanometers to about 400 nanometers. In anembodiment, energy-emitting component 902 comprises a peak emissionwavelength ranging from about 100 nanometers to about 320 nanometers. Inan embodiment, energy-emitting component 902 comprises a peak emissionwavelength ranging from about 280 nanometers to about 320 nanometers.

In an embodiment, the system 100 includes at least one activelycontrollable excitation component 910 including one or more energyemitters 302. In an embodiment, the actively controllable excitationcomponent 910 is configured to deliver at least one of anelectromagnetic sterilizing energy stimulus, an electrical sterilizingenergy stimulus, an ultrasonic sterilizing energy stimulus, and athermal sterilizing energy stimulus. In an embodiment, the activelycontrollable excitation component 910 is operable to emit a sterilizingenergy stimulus having one or more peak emission wavelengths in theinfrared, visible, or ultraviolet spectrum, or combinations thereof. Inan embodiment, the actively controllable excitation component 910includes one or more energy emitters 302 configured to deliver at leastone of an electrical sterilizing energy stimulus, an electromagneticsterilizing energy stimulus, an ultrasonic sterilizing energy stimulus,and a thermal sterilizing energy stimulus of sufficient strength orduration to attenuate an activity of an infectious agent proximate theouter portion of the one or more fluid-flow passageways. In anembodiment, the actively controllable excitation component 910 includesone or more energy emitters 302 configured to deliver at least one of anelectrical sterilizing energy stimulus, an electromagnetic sterilizingenergy stimulus, an ultrasonic sterilizing energy stimulus, and athermal sterilizing energy stimulus of sufficient strength or durationto cause the death of one or more pathogens proximate the outer portionof the one or more fluid-flow passageways. In an embodiment, theactively controllable excitation component 910 includes one or moreenergy emitters 302 configured to deliver a sufficient amount of atleast one of an electrical sterilizing energy stimulus, anelectromagnetic sterilizing energy stimulus, an ultrasonic sterilizingenergy stimulus, and a thermal sterilizing energy stimulus, in vivo, toinduce PCD without substantially inducing necrosis of an infectiousagent proximate the outer portion of the one or more fluid-flowpassageways.

In an embodiment, the actively controllable excitation component 910includes a spatially patterned energy-emitting element 912 configured toprovide a spatially patterned energy stimulus. In an embodiment, theactively controllable excitation component 304 includes a spatiallypatterned energy-emitting element configured to provide a spatiallypatterned energy stimulus, the spatially patterned energy-emittingelement 912 having a plurality of spaced apart energy emitters 302. Inan embodiment, the actively controllable excitation component 910includes at least one energy-emitting component 902, the at least oneenergy-emitting component 902 configured to provide a spatiallypatterned light energy stimulus.

In an embodiment, the actively controllable excitation component 910includes one or more spatially patterned energy-emitting elements 914configured to provide a spatially patterned energy stimulus. In anembodiment, at least one spatially patterned energy-emitting element 914includes a plurality of spaced-apart energy emitters 202. The activelycontrollable excitation component 910 can include, but is not limitedto, at least one patterned electrode 916. In an embodiment, at least onepatterned electrode 916 is configured to provide a spatially patternedenergy stimulus. In an embodiment, the power source 902 iselectromagnetically, magnetically, ultrasonically, optically,inductively, electrically, or capacitively coupleable to the activelycontrollable excitation component 910.

In an embodiment, the implantable device 102 includes one or moreactively controllable excitation components 910 configured to deliverand energy stimulus to a region proximate at least one of an outersurface 108 and an inner surface 110 of the body structure 104. In anembodiment, the implantable device 102 includes one or more activelycontrollable excitation components 910 configured to deliver and energystimulus to an interior of one or more fluid-flow passageways 106. In anembodiment, the implantable device 102 includes one or more activelycontrollable excitation components 304 configured to deliver and energystimulus to an exterior of the body structure 104. In an embodiment, theimplantable device 102 includes one or more actively controllableexcitation components 910 configured to deliver energy to a regionwithin the biological subject. In an embodiment, an average integratedenergy flux of the actively controllable excitation component 910 isless than about 80 milli-joules per square centimeter. In an embodiment,average integrated energy flux of the actively controllable excitationcomponent 910 is less than about 35 milli-joules per square centimeter.In an embodiment, an average integrated energy flux of the activelycontrollable excitation component 910 is less than about 15 milli-joulesper square centimeter. In an embodiment, an average energy density ofthe actively controllable excitation component 910 ranges from aboutless than about 15 milli-joules per square centimeter to about less thanabout 80 milli joules per square centimeter.

In an embodiment, the system 100 includes at least one controller 402operably coupled to the actively controllable excitation component 910.In an embodiment, the at least one controller 402 is configured tocontrol at least one parameter associated with the delivery of theenergy stimulus. In an embodiment, the system 100 includes at least onesensor 442 and at least one controller 402 operably coupled to theactively controllable excitation component 910. In an embodiment, the atleast one controller 402 is configured to control at least one parameterassociated with the delivery of the energy stimulus based on a detectedparameter.

In an embodiment, actively controllable excitation component 910 isconfigured to reduce the concentration of an infectious agent in theimmediate vicinity of an implant. In an embodiment, the activelycontrollable excitation component 910 is operable to concurrently orsequentially deliver at least a first sterilizing energy stimulus and asecond sterilizing energy stimulus, in vivo, to tissue proximate thefirst outer surface 108. In an embodiment, at least one of the firststerilizing energy stimulus and the second sterilizing energy stimuluscomprises a peak emission wavelength in the x-ray, ultraviolet, visible,infrared, near infrared, terahertz, microwave, or radio frequencyspectrum; and a controller 402 communicatively coupled to the activelycontrollable excitation component 910, the controller 402 configured toregulate at least one parameter associated with the delivery of asterilizing energy stimulus.

In an embodiment, the second energy stimulus comprises at least one ofan illumination intensity, an energy-emitting pattern, a peak emissionwavelength, an ON-pulse duration, an OFF-pulse duration, and a pulsefrequency different from the first energy stimulus. In an embodiment,the actively controllable excitation component 910 is configured toconcurrently or sequentially generate at least a first sterilizingenergy stimulus and a second sterilizing energy stimulus. In anembodiment, one or more controllers 402 are configured to control atleast one parameter associated with the delivery of at least one of thefirst sterilizing energy stimulus and the second sterilizing energystimulus. For example, in an embodiment, at least one controller 402 isconfigured to control at least one of an excitation intensity, anexcitation frequency, an excitation pulse frequency, an excitation pulseratio, an excitation pulse intensity, an excitation pulse duration time,and an excitation pulse repetition rate associated with the delivery ofat least one of the first sterilizing energy stimulus and the secondsterilizing energy stimulus. In an embodiment, at least one controller402 is configured to control at least one of a first and a secondsterilizing energy stimulus delivery regimen parameter, a temporalsterilizing energy stimulus delivery pattern parameter, a spaced-apartsterilizing energy stimulus delivery pattern parameter, a spatialelectric field modulation parameter, a spatial electric field magnitudeparameter, a spatial electric field distribution parameter, an ON-rate,or an OFF-rate associated with the delivery of at least one of the firststerilizing energy stimulus and the second sterilizing energy stimulus.In an embodiment, at least one controller 402 is configured to controlat least one parameter associated with the delivery of the firststerilizing energy stimulus, and at least one other controller 402 isconfigured to control at least one parameter associated with thedelivery of the second sterilizing stimulus.

In an embodiment, actively controllable excitation component 910 isenergetically, electrically, photonically, thermally or ultrasonicallycoupleable, via one or more waveguides 920, to an exterior 108 of theimplantable device 102. In an embodiment, actively controllableexcitation component 910 is energetically, electrically, photonically,thermally or ultrasonically coupleable, via one or more waveguides 920,to an interior 110 of at least one of the one or more fluid-flowpassageways 106. In an embodiment, actively controllable excitationcomponent 910 includes at least one of an ultrasonic energy waveguide922, an optical energy waveguide 924, an electromagnetic energywaveguide 926, and the like.

In an embodiment, the actively controllable excitation component 910 isconfigured to provide a voltage across a region proximate theimplantable device 102 from a power source 700 coupled to theimplantable device 102. In an embodiment, the voltage is sufficient toexceed a nominal dielectric strength of a cell plasma membrane withoutsubstantially interfering with a normal operation of the implantabledevice 102. In an embodiment, the voltage is sufficient to reduce theconcentration of an infectious agent in the immediate vicinity of animplant.

Referring to FIG. 10, in an embodiment, the system 100 includes acontrol means 1000. The control means 1000 can include for example, butnot limited to, electrical, electromechanical, software, firmware, orother control components, or combinations thereof. In an embodiment, thecontrol means 1000 includes electrical circuitry configured to forexample, but not limited to, control at least one of an energy stimulusdelivery regimen parameter, a temporal sterilizing energy stimulusdelivery pattern parameter, a spaced-apart energy stimulus deliverypattern parameter, a spatial energy stimulus modulation parameter, aspatial energy stimulus magnitude parameter, and a spatial energystimulus distribution parameter associated with the delivery of theenergy stimulus. In an embodiment, the control means 1000 includeselectrical circuitry configured to for example, but not limited to,control the one or more controllable-release ports configured to deliverthe at least one scaffold-forming material to the first outer surface108. Further non-limiting examples of circuitry can be found, amongother things, in U.S. Pat. No. 7,236,821 (issued Jun. 26, 2001), thecontents of which is incorporated herein by reference.

In a general sense, those skilled in the art will recognize that thevarious aspects described herein (which can be implemented, individuallyand/or collectively, by a wide range of hardware, software, firmware,and/or any combination thereof) can be viewed as being composed ofvarious types of “electrical circuitry.” Consequently, as used herein“electrical circuitry” includes, but is not limited to, electricalcircuitry having at least one discrete electrical circuit, electricalcircuitry having at least one integrated circuit, electrical circuitryhaving at least one application specific integrated circuit, electricalcircuitry forming a general purpose computing device configured by acomputer program (e.g., a general purpose computer configured by acomputer program which at least partially carries out processes and/ordevices described herein, or a microprocessor configured by a computerprogram which at least partially carries out processes and/or devicesdescribed herein), electrical circuitry forming a memory device (e.g.,forms of memory (e.g., random access, flash, read only, etc.)), and/orelectrical circuitry forming a communications device (e.g., a modem,communications switch, optical-electrical equipment, etc.). Those havingskill in the art will recognize that the subject matter described hereincan be implemented in an analog or digital fashion or some combinationthereof.

In an embodiment, the control means 1000 includes one or moreelectro-mechanical systems configured to for example, control at leastone of a sterilizing stimulus delivery regimen parameter, a temporalsterilizing energy stimulus delivery pattern parameter, a spaced-apartsterilizing stimulus delivery pattern parameter, a spatial sterilizingstimulus modulation parameter, a spatial sterilizing stimulus magnitudeparameter, and a spatial sterilizing stimulus distribution parameterassociated with the delivery of the sterilizing stimulus. In anembodiment, the control means 1000 includes one or moreelectro-mechanical systems configured to for example, but not limitedto, control the one or more controllable-release ports configured todeliver the at least one active agent to the first outer surface 108. Ina general sense, the various embodiments described herein can beimplemented, individually and/or collectively, by various types ofelectro-mechanical systems having a wide range of electrical componentssuch as hardware, software, firmware, and/or virtually any combinationthereof; and a wide range of components that can impart mechanical forceor motion such as rigid bodies, spring or torsional bodies, hydraulics,electro-magnetically actuated devices, and/or virtually any combinationthereof.

Consequently, as used herein “electro-mechanical system” includes, butis not limited to, electrical circuitry operably coupled with atransducer (e.g., an actuator, a motor, a piezoelectric crystal, a MicroElectro Mechanical System (MEMS), etc.), electrical circuitry having atleast one discrete electrical circuit, electrical circuitry having atleast one integrated circuit, electrical circuitry having at least oneapplication specific integrated circuit, electrical circuitry forming ageneral purpose computing device configured by a computer program (e.g.,a general purpose computer configured by a computer program which atleast partially carries out processes and/or devices described herein,or a microprocessor configured by a computer program which at leastpartially carries out processes and/or devices described herein),electrical circuitry forming a memory device (e.g., forms of memory(e.g., random access, flash, read only, etc.)), electrical circuitryforming a communications device (e.g., a modem, communications switch,optical-electrical equipment, etc.), and/or any non-electrical analogthereto, such as optical or other analogs. Non-limiting examples ofelectro-mechanical systems include a variety of consumer electronicssystems, medical devices, as well as other systems such as motorizedtransport systems, factory automation systems, security systems, and/orcommunication/computing systems. The term, electro-mechanical, as usedherein is not necessarily limited to a system that has both electricaland mechanical actuation except as context may dictate otherwise.

In an embodiment, the system 100 includes a control means 1000 foroperably coupling to at least one of a plurality of energy emitters 302,an energy emitting component 902, an actively controllable excitationcomponent 910, and the like. In an embodiment, the control means 1000 isoperable to control at least one component associated with the deliveryof an energy stimulus. Such components can include for example, but notlimited to, a delivery regimen component 1004, a spaced-apart energystimulus delivery pattern component 1006, a spatial energy stimulusmodulation component 1008, a spatial energy stimulus magnitude component1010, a spatial energy stimulus distribution component 1012, or thelike. In an embodiment, the control means 1000 is operable to control atleast one of a spatial illumination field modulation component 1014, aspatial illumination field intensity component 1016, and a spatialillumination delivery pattern component 1018. In an embodiment, thecontrol means 1000 is operable to control at least one sterilizingstimulus delivery regimen parameter selected from an excitationintensity, an excitation frequency, an excitation pulse frequency, anexcitation pulse ratio, an excitation pulse intensity, an excitationpulse duration time, an excitation pulse repetition rate, an ON-rate, oran OFF-rate. A “duty cycle” includes, but is not limited to, a ratio ofa pulse duration (τ) relative to a pulse period (T). For example, apulse train having a pulse duration of 10 as and a pulse signal periodof 40 as, corresponds to a duty cycle (D=τ/T) of 0.25. In an embodiment,the control means 1000 is operable to manage a duty cycle associatedwith emitting an effective amount of the electrical sterilizing stimulusfrom the actively controllable excitation component 910.

In an embodiment, the control means 1000 is operable to control at leastone component 1020 associated with the delivery of an active agent. Suchcomponents can include for example, but not limited to, a delivery ratecomponent, a delivery amount component, a delivery compositioncomponent, a port release rate component, a port release amountcomponent, a port release pattern component, or the like.

The control means 1000 can include, but is not limited to, one or morecontrollers 402 such as a processor (e.g., a microprocessor) 404, acentral processing unit (CPU) 406, a digital signal processor (DSP) 408,an application-specific integrated circuit (ASIC) 410, a fieldprogrammable gate array 412, and the like, and combinations thereof, andcan include discrete digital and/or analog circuit elements orelectronics. In an embodiment, the control means 1000 is configured towirelessly couple to an implantable device 102 that communicates viawireless communication with the control means 1000. Non-limitingexamples of wireless communication include optical connections, audio,ultraviolet connections, infrared, BLUETOOTH®, Internet connections,network connections, and the like.

In an embodiment, the control means 1000 includes at least onecontroller 402 and at least one sensor component 440. In an embodiment,the at least one controller 402 is communicably coupled to at least oneof the actively controllable excitation component 910 and the sensorcomponent 440, and is configured to control at least one parameterassociated with the delivery of an energy stimulus based on detectedinformation associated with the sensor component 440.

In an embodiment, the control means 1000 is operably coupled to the oneor more sensors 442, and is configured to determine the at least onecharacteristic associated with the tissue proximate the implantabledevice 102. In an embodiment, the control means 1000 is configured toperform a comparison of the at least one characteristic associated withthe tissue proximate the implantable device 102 to stored referencedata, and to generate a response based at least in part on thecomparison.

In an embodiment, the control means 1000 is operably coupled to the oneor more sensors 442, and is configured to determine the at least onephysiological characteristic of the biological subject. In anembodiment, the control means 1000 is configured to perform a comparisonof the determined at least one physiological characteristic of thebiological subject to stored reference data, and to generate a responsebased at least in part on the comparison. In an embodiment, thegenerated response includes at least one of a response signal, a changeto a sterilizing stimulus parameter, a change in an excitationintensity, a change in an excitation frequency, a change in anexcitation pulse frequency, a change in an excitation pulse ratio, achange in an excitation pulse intensity, a change in an excitation pulseduration time, a change in an excitation pulse repetition rate, and achange in a sterilizing stimulus delivery regimen parameter.

In an embodiment, the control means 1000 includes at least onecontroller 402, which is communicably coupled to the activelycontrollable excitation component 910. In an embodiment, the controlmeans 1000 is configured to control at least one of a duration time, anamount of energy, an excitation amount, an excitation type, a deliverylocation, and a spatial-pattern stimulation configuration associatedwith the delivery of the energy stimulus.

The control means 1000 can include, but is not limited to, one or morememories 414 that store instructions or data, for example, volatilememory (e.g., random access memory (RAM) 416, dynamic random accessmemory (DRAM), or the like) non-volatile memory (e.g., read-only memory(ROM) 418, electrically erasable programmable read-only memory (EEPROM),compact disc read-only memory (CD-ROM), or the like), persistent memory,and the like. Further non-limiting examples of one or more memories 414include erasable programmable read-only memory (EPROM), flash memory,and the like. The one or more memories can be coupled to, for example,one or more controllers by one or more instruction, data, or powerbuses.

The control means 1000 can include a computer-readable media drive ormemory slot 426, and one or more input/output components 428 such as,for example, a graphical user interface, a display, a keyboard, akeypad, a trackball, a joystick, a touch-screen, a mouse, a switch, adial, and the like, and any other peripheral device. The control means1000 can further include one or more databases 422, and one or more datastructures 424. The computer-readable media drive or memory slot can beconfigured to accept computer-readable memory media. In an embodiment, aprogram for causing the system 100 to execute any of the disclosedmethods can be stored on a computer-readable recording medium.Non-limiting examples of computer-readable memory media include CD-R,CD-ROM, DVD, flash memory, floppy disk, hard drive, magnetic tape,magnetooptic disk, MINIDISC, non-volatile memory card, EEPROM, opticaldisk, optical storage, RAM, ROM, system memory, web server, and thelike.

In an embodiment, the control means 1000 is adapted to apply a potentialacross a plurality of energy emitters 302 having parameters selected toproduce superoxide species in an interstitial fluid proximate theplurality of energy emitters 302 when the implantable device 102 isimplanted within the biological subject. In an embodiment, the appliedpotential is sufficient to produce superoxide species in an interstitialfluid proximate the plurality of energy emitters 302 when theimplantable device 102 is implanted within the biological subject.

FIG. 11 shows a system 100 in which one or more methodologies ortechnologies can be implemented such as, for example, managing atransport of biological fluids, delivering energy stimuli, and activelydetecting, treating, or preventing an infection, or the like. In anembodiment, the implantable device 102 includes means for reflecting1102 at least a portion of an emitted energy stimulus within an interiorof at least one of the one or more fluid-flow passageways 106. In anembodiment, the means for reflecting 1102 an emitted energy stimulusincludes one or more reflective materials, one or more waveguides 920,and one or more controllers 402. In an embodiment, the means forreflecting 1102 an emitted energy stimulus can include one or moremechanical components, electro-mechanical components for generating,transmitting, or receiving waves (e.g., ultrasonic waves,electromagnetic waves, or the like), or the like.

The one or more waveguides 920 can take a variety of shapes,configurations, and geometric including, but not limited to,cylindrical, conical, planar, parabolic, regular or irregular forms. Inan embodiment, two or more optical waveguides 920 can be coupled (e.g.,optically coupled) to form, for example, an array of waveguides 920. Inan embodiment, the waveguide 920 comprises a laminate including one ormore optically active coatings. In an embodiment, two or more opticalwaveguides 920 can be arranged to form a part of patterned energyemitting component. In an embodiment, multiple optical waveguides 920are formed from a single substrate or structure. Waveguides 920 caninclude any structure suitable to directing electromagnetic energywaves. Non-limiting examples of waveguides 920 include electromagneticwaveguides, optical waveguides (e.g., optical fibers, photonic-crystalfibers, or the like), acoustic waveguides (e.g., ultrasonic energywaveguides), multi-energy waveguides, or the like. Further non-limitingexamples of waveguides 920 include lens structures, light-diffusingstructures, mirror structures, mirrored surfaces, reflective coatings,reflective materials, reflective surfaces, or combinations thereof.Further non-limiting examples of waveguides include etchings, facets,grooves, thin-films, optical micro-prisms, lenses (e.g., micro-lenses,or the like), diffusing elements, diffractive elements (e.g., gratings,cross-gratings, or the like), texturing, and the like.

In an embodiment, one or more energy emitters 302 are energeticallycoupled to the exterior or interior surfaces 108, 110 of a bodystructure 104 via one or more waveguides 920. In an embodiment, aportion of the exterior surface 108 or interior surface 110 of a bodystructure 104 includes a mirrored or reflective surfaces such as, forexample, a film, a coating, an optically active coating, a mirrored orreflective substrate, or the like. In an embodiment, the one or morewaveguides 920 include at least one of a transparent, translucent, orlight-transmitting material, and combinations or composites thereof.Among transparent, translucent, or light-transmitting materials,examples include those materials that offer a low optical attenuationrate to the transmission or propagation of light waves. Examples oftransparent, translucent, or light-transmitting materials include butare not limited to crystals, epoxies, glasses, borosilicate glasses,optically clear materials, semi-clear materials, plastics, thermoplastics, polymers, resins, thermal resins, and the like, orcombinations or composites thereof. In an embodiment, the one or morewaveguides 920 include at least one of an optically transparent,optically translucent, and light-transmitting component. In anembodiment, the one or more waveguides 920 include at least oneoptically transparent, translucent, or light-transmitting material.

Non-limiting examples of optically transparent, translucent, orlight-transmitting material include one or more of acetal copolymers,acrylic, glass, AgBr, AgCl, Al₂O₃, GeAsSe glass, BaF₂, CaF₂, CdTe,AsSeTe glass, CsI, diamond, GaAs, Ge, ITRAN materials, KBr, thalliumbromide-Iodide, LiF, MgF₂, NaCl, polyethylene, Pyrex, Si, SiO₂, ZnS,ZnSe, thermoplastic polymers, or thermoset polymers, or compositesthereof.

Further non-limiting examples of optically transparent, translucent, orlight-transmitting material include one or more of acrylonitrilebutadiene styrene polymers, cellulosic, epoxy, ethylene butyl acrylate,ethylene tetrafluoroethylene, ethylene vinyl alcohol, fluorinatedethylene propylene, furan, nylon, phenolic,poly[2,2,4-trifluoro-5-trifluoromethoxy-1,3-dioxole-co-tetroafluoroethylene],poly[2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole-co-tetrafluoroethylene],poly[2,3-(perfluoroalkenyl)perfluorotetrahydrofuran], polyacrylonitrilebutadiene styrene, polybenzimidazole, polycarbonate, polyester,polyetheretherketone, polyetherimide, polyethersulfone, polyethylene,polyimide, polymethyl methacrylate, polynorbornene,polyperfluoroalkoxyethylene, polystyrene, polysulfone, polyurethane,polyvinyl chloride, polyvinylidene fluoride, diallyl phthalate,thermoplastic elastomer, transparent polymers, or vinyl ester, orcomposites thereof.

In an embodiment, at least a portion of a body structure 104 definingthe one or more fluid-flow passageways 106 includes one or more activelycontrollable reflective or transmissive components 1104 configured tooutwardly transmit or internally reflect an energy stimulus propagatedthrough at least one of the one or more fluid-flow passageways 106. Inan embodiment, a controller 402 is operably coupled to at least one ofthe one or more actively controllable reflective and transmissivecomponents 1104. In an embodiment, a controller 402 is configured tocause an outward-transmission or internal-reflection of an energystimulus propagated through at least one of the one or more fluid-flowpassageways 106 based on, for example, detected information from asensor component 440.

In an embodiment, the implantable device 102 includes means forreflecting at least a portion of an emitted energy stimulus within aninterior of at least one of the one or more fluid-flow passageways 106.In an embodiment, the means for reflecting at least a portion of anemitted energy stimulus includes at least one waveguide 920, one or moreenergy emitters 302, and one or more controllers 402. In an embodiment,the implantable device 102 includes means for laterally reflecting orlongitudinally reflecting electromagnetic radiation transmitted withinan interior of at least one of the one or more fluid-flow passageways106. In an embodiment, means for laterally reflecting or longitudinallyreflecting electromagnetic radiation includes at least one waveguide920, one or more energy emitters 302, and one or more controllers 402.

In an embodiment, at least a portion of a body structure 104 definingthe one or more fluid-flow passageways 106 includes an optical materialthat permits the transmission of at least a portion of an emitted energystimulus from an interior of at least one of the one or more fluid-flowpassageways 106 to an exterior of at least one of the one or morefluid-flow passageways 106. In an embodiment, at least a portion of abody structure 104 defining the one or more fluid-flow passagewaysincludes an optical material that internally reflects at least a portionof an emitted energy stimulus present within an interior of at least oneof the one or more fluid-flow passageways 106. In an embodiment, atleast a portion of a body structure 104 defining the one or morefluid-flow passageways 106 includes an optical material that internallyreflects at least a portion of an emitted energy stimulus within aninterior of at least one of the one or more fluid-flow passageways 106,without substantially permitting the transmission of the emitted energystimulus through an exterior of the body structure.

In an embodiment, the implantable device 102 includes one or moreoptical materials forming at least a portion of a body structure 104defining the one or more fluid-flow passageways 106. In an embodiment,the one or more optical materials are configured to limit an amount ofthe energy stimulus that can traverse within the one or more fluid-flowpassageways 106 and through an outer surface 108 of the body structure104. In an embodiment, the implantable device 102 includes one or moreoptical materials on at least a portion of a body structure 104 definingthe one or more fluid-flow passageways 106 to internally reflect atleast a portion of an emitted energy stimulus from the one or moreenergy emitters 302 into an interior of at least one of the one or morefluid-flow passageways 106. In an embodiment, the implantable device 102includes at least one outer internally reflective coating 1108 on a bodystructure 104 defining the one or more fluid-flow passageways 106. In anembodiment, the implantable device 102 includes at least one innerinternally reflective coating 1110 on a body structure 104 defining theone or more fluid-flow passageways 106.

In an embodiment, at least a portion of the one or more fluid-flowpassageways 106 includes an optical material that internally directs atleast a portion of an emitted energy stimulus along a substantiallylongitudinal direction of at least one of the one or more fluid-flowpassageways 106. In an embodiment, at least a portion of the one or morefluid-flow passageways 106 includes an optical material that internallydirects at least a portion of an emitted energy stimulus along asubstantially lateral direction of at least one of the one or morefluid-flow passageways 106.

In an embodiment, at least one of the one or more fluid-flow passageways106 includes a surface configured to laterally internally reflect orlongitudinally internally reflect electromagnetic radiation transmittedtherethrough. For example, in an embodiment, at least a portion of abody structure defining the one or more fluid-flow passageways 106includes a reflective surface 1112 capable of reflecting at least about50 percent of an energy stimulus emitted by the one or more energyemitters that impinges on the reflective surface. In an embodiment, atleast a portion of a body structure defining the one or more fluid-flowpassageways 106 includes a reflective surface 1112 that is reflective ata first wavelength and transmissive at a second wavelength differentthan the first wavelength. In an embodiment, at least one of the one ormore fluid-flow passageways 106 includes one or more internallyreflective components 1114 configured to manage a delivery of light to abiological fluid received within the one or more fluid-flow passageways106, and to manage a collection of reflected light from the biologicalfluid.

In an embodiment, at least a portion of the one or more fluid-flowpassageways 106 includes an optical component 1120 that directs a firstportion of an emitted energy stimulus along a substantially lateraldirection in one or more regions of at least one of the one or morefluid-flow passageways 106 and an optical component 1122 that directs asecond portion of the emitted energy stimulus along a substantiallylongitudinal direction in one or more regions of at least one of the oneor more fluid-flow passageways 106. In an embodiment, at least a portionof the one or more fluid-flow passageways 106 includes a first opticalcomponent configured to direct at least a portion of an emitted energystimulus along a substantially lateral direction in a first region of atleast one of the one or more fluid-flow passageways 106 and a secondoptical component configured to direct at least a portion of the emittedenergy stimulus along a substantially lateral direction in a secondregion of the one or more fluid-flow passageways 106, the second regiondifferent from the first region. In an embodiment, at least a portion ofthe one or more fluid-flow passageways 106 includes a first opticalcomponent that directs at least a portion of an emitted energy stimulusalong a substantially longitudinal direction in a first region of atleast one of the one or more fluid-flow passageways 106 and a secondoptical component that directs at least a portion of the emitted energystimulus along a substantially longitudinal direction in a second regionof the one or more fluid-flow passageways 106, the second regiondifferent from the first region. In an embodiment, at least a portion ofthe one or more fluid-flow passageways 106 includes a first opticalcomponent configured to direct at least a portion of an emitted energystimulus along a substantially lateral direction in a first region of atleast one of the one or more fluid-flow passageways 106 and a secondoptical component configured to direct at least a portion of the emittedenergy stimulus along a substantially lateral direction in a secondregion of the one or more fluid-flow passageways 106, the second regiondifferent from the first region.

In an embodiment, at least one of the one or more fluid-flow passageways106 includes at least one of an outer surface and an inner surface thatis reflective to at least one of electromagnetic energy, ultrasonicenergy, and thermal energy. In an embodiment, at least one of the one ormore fluid-flow passageways 106 includes an inner surface that isinternally reflective to electromagnetic radiation. In an embodiment, atleast one of the one or more fluid-flow passageways 106 includes asurface that is internally reflective to ultraviolet radiation. In anembodiment, at least one of the one or more fluid-flow passageways 106includes a surface that is internally reflective to infrared radiation.In an embodiment, at least one of the one or more fluid-flow passageways106 includes a surface having a reflective coating.

In an embodiment, at least one of the one or more fluid-flow passageways106 includes a reflective material. In an embodiment, the reflectivematerial comprises at least one of aluminum, barium sulfate, gold,silver, titanium dioxide, and zinc oxide. In an embodiment, at least oneof the one or more fluid-flow passageways 106 includes an ultravioletenergy reflective material. In an embodiment, the ultraviolet energyreflective material comprises barium sulfate.

In an embodiment, at least a portion of a body structure 104 definingthe one or more fluid-flow passageways 106 includes an opticaltransparent, optical translucent, or light-transmitting component 1124that directs at least a portion of an emitted energy stimulus into aninterior of at least one of the one or more fluid-flow passageways 106.In an embodiment, the optical transparent, optical translucent, orlight-transmitting component 1124 includes one or more waveguides 920.In an embodiment, the optical transparent, optical translucent, orlight-transmitting component 1124 includes one or more optical energywaveguides 920. In an embodiment, the optical transparent, opticaltranslucent, or light-transmitting component 1124 comprises alight-transmitting material. In an embodiment, the optical transparent,optical translucent, or light-transmitting component 1124 comprises oneor more optical fibers. In an embodiment, the optical transparent,optical translucent, or light-transmitting component 1124 extendssubstantially longitudinally along at least one of the one or morefluid-flow passageways 106. In an embodiment, the optical transparent,optical translucent, or light-transmitting component 1124 extendssubstantially laterally within at least one of the one or morefluid-flow passageways 106. In an embodiment, the optical transparent,optical translucent, or light-transmitting component 1124 extendssubstantially helically within at least one of the one or morefluid-flow passageways 106.

In an embodiment, the implantable device 102 includes one or moreoptical waveguides 920 received within at least one of the one or morefluid-flow passageways 106. In an embodiment, the one or more opticalwaveguides 920 are photonically coupleable to at least one of the one ormore energy emitters 302 and configured to direct an emitted energystimulus into an interior of at least one of the one or more fluid-flowpassageways 106.

Referring to FIG. 12, the system 100 can include one or more implantabledevices 102 including for example, but not limited to, circuitryconfigured to obtain information 1202, and circuitry configured to storethe obtained information 1204. In an embodiment, the circuitryconfigured to obtain information 1202 includes circuitry configured toobtain information associated with a delivery of the energy stimulus. Inan embodiment, the circuitry configured to obtain information 1202includes circuitry configured to obtain at least one of a commandstream, a software stream, and a data stream. In an embodiment, thecircuitry configured to obtain information includes at least one of areceiver and a transceiver configured to obtain information regarding atarget detection set of one or more characteristics associated with thebiological subject.

The implantable device 102 can include, but is not limited to, one ormore controllers 402 configured to perform a comparison of, for example,a characteristic associated with a biological subject to obtainedinformation, and to generate a response based at least in part on thecomparison. In an embodiment, the generated response includes causingthe obtained information to be stored in one or more data structures424.

The system 100 can include one or more implantable devices 102 includingfor example, but not limited to, one or more receivers 1206,transceivers 1208, or transmitters 1210. In an embodiment, at least oneof the one or more receiver 1206, transceivers 1208, and transmitters1210, can be, for example, wirelessly coupled to a controller 402 thatcommunicates with a control unit of the system 100 via wirelesscommunication. In an embodiment, at least one of the one or morereceivers 1206 and transceivers 1208 is configured to acquireinformation associated with a set of targets, markers, or the like fordetection. In an embodiment, at least one of the one or more receivers1206 and transceivers 1208 is configured to acquire informationassociated with a set of physiological characteristic for detection. Inan embodiment, at least one of the one or more receivers 1206 andtransceivers 1208 is configured to acquire information associated withone or more physiological characteristics for detection. In anembodiment, at least one of the one or more receivers 1206 andtransceivers 1208 is configured to acquire information associated withone or more cerebrospinal fluid characteristics for detection.

In an embodiment, at least one receiver 1206 is configured to acquireinformation associated with a delivery of an energy stimulus. In anembodiment, the at least one receiver 1206 is configured to acquiredata. In an embodiment, the at least one receiver 1206 is configured toacquire software. In an embodiment, the at least one receiver 1206 isconfigured to receive data from one or more distal sensors 442. In anembodiment, the at least one receiver 1206 is configured to receivestored reference data. In an embodiment, the at least one receiver 1206is configured to acquire at least one of instructions, instructionsassociated with a delivery of an energy stimulus, instructionsassociated with a delivery of an active agent, information associatedwith a biological sample, instructions associated with a biologicalfluid, instructions associated with a disease state, and the like.

In an embodiment, the at least one receiver 1206 is configured toacquire information based at least in part on a detected characteristicassociated with a cerebrospinal fluid received within at least one ofthe one or more fluid-flow passageways 106. In an embodiment, the atleast one receiver 1206 is configured to acquire information based atleast in part on a detected characteristic associated with a tissueproximate the one or more fluid-flow passageways 106. In an embodiment,the at least one receiver 1206 is configured to acquire informationbased at least in part on a detected physiological characteristicassociated with the biological subject. In an embodiment, the at leastone receiver 1206 is configured to acquire information associated withdelivery of an active agent.

In an embodiment, the system 100 includes one or more receivers 1206configured to acquire spectral information (e.g., radio frequency (RF)information) emitted by an in vivo biological sample. In an embodiment,the one or more receivers 1206 include one or more of analog-to-digitalconverters, signal amplifier, matching networks, oscillators, poweramplifiers, RF receive coils, RF synthesizers, or signal filters. In anembodiment, the system 100 includes one or more transceivers 1208 (e.g.,RF transceivers 1208) configured to generate RF excitation pulses thatinteracts with, for example, an in vivo target.

The system 100 can include one or more implantable devices 102 includingfor example, but not limited to, circuitry for providing information1212. In an embodiment, the circuitry for providing information 1212includes circuitry for providing status information regarding theimplantable device. In an embodiment, the circuitry for providinginformation 1212 includes circuitry for providing information regardingat least one characteristic associated with a biological subject. Forexample, in an embodiment, the circuitry for providing information 1212includes circuitry for providing information regarding at least onecharacteristic associated with a tissue or biological fluid proximatethe implantable device 102. In an embodiment, the circuitry forproviding information includes circuitry for providing informationregarding at least one physiological characteristic associated with thebiological subject. In an embodiment, the circuitry for providinginformation 1212 includes circuitry for providing information regardingat least one characteristic associated with the cerebrospinal fluid ofthe biological subject. In an embodiment, the circuitry for providinginformation 1212 includes circuitry for providing information regardingat least one characteristic associated with a tissue proximate the oneor more fluid-flow passageways 106.

The system 100 can include one or more implantable devices 102 includingfor example, but not limited to, at least one transmitter 1210configured to send information. The system 100 can include one or moreimplantable devices 102 including for example, but not limited to,circuitry for transmitting information. In an embodiment, the at leastone transmitter 1210 is configured to send information based at least inpart on a detected characteristic associated with a cerebrospinal fluidreceived within at least one of the one or more fluid-flow passageways106. In an embodiment, the at least one transmitter 1210 is configuredto send a request for transmission of at least one of data, a command,an authorization, an update, and a code

The system 100 can include one or more implantable devices 102 includingfor example, but not limited to, one or more cryptographic logiccomponents 1216. In an embodiment, at least one of the one or morecryptographic logic components 1216 is configured to implement at leastone cryptographic process, or cryptographic logic, or combinationsthereof. Non-limiting examples of a cryptographic process include one ormore processes associated with cryptographic protocols, decryptionprotocols, encryption protocols, regulatory compliance protocols (e.g.,FDA regulatory compliance protocols, or the like), regulatory useprotocols, authentication protocols, authorization protocols, treatmentregimen protocols, activation protocols, encryption protocols,decryption protocols, and the like. Non-limiting examples of acryptographic logic include one or more crypto-algorithms signal-bearingmedia, crypto controllers (e.g., crypto-processors), cryptographicmodules (e.g., hardware, firmware, or software, or combinations thereoffor implementing cryptographic logic, or cryptographic processes), andthe like.

In an embodiment, the cryptographic logic component 1216 is configuredto implement at least one cryptographic process or cryptographic logic.In an embodiment, the cryptographic logic component 1216 is configuredto implement one or more processes associated with at least one of acryptographic protocol, a decryption protocol, an encryption protocol, aregulatory compliance protocol, a regulatory use protocol, anauthentication protocol, an authorization protocol, a delivery protocol,an activation protocol, an encryption protocol, and a decryptionprotocol. In an embodiment, the cryptographic logic component 1216includes one or more crypto-algorithms, signal-bearing media, cryptocontrollers, or cryptographic modules.

In an embodiment, the cryptographic logic component 1216 is configuredto generate information associated with at least one of anauthentication protocol, an authorization protocol, a delivery protocol(e.g., a sterilizing energy stimulus delivery protocol), an activationprotocol, an encryption protocol, and a decryption protocol. In anembodiment, the cryptographic logic component 1216 is configured togenerate information associated at least one of an authorizationinstruction, an authentication instruction, a prescription dosinginstruction, a sterilizing energy stimulus administration instruction,and a prescribed regimen instruction.

In an embodiment, the cryptographic logic component 1216 is configuredto generate information associated with at least one of an instructionstream, an encrypted data stream, an authentication data stream, and anauthorization data stream. In an embodiment, the cryptographic logiccomponent 1216 is configured to generate information associated with atleast one of an activation code, an error code, a command code, and anauthorization code. In an embodiment, the cryptographic logic component1216 is configured to generate information associated with at least oneof a cryptographic protocol, a decryption protocol, an encryptionprotocol, a regulatory compliance protocol, and regulatory use protocol.

Referring to FIG. 13, in an embodiment, the implantable device 102includes a body structure 104 including one or more components 1302 thatare energetically actuatable between an optically transparent state andan optically reflective state.

In an embodiment, an indwelling shunt apparatus includes a bodystructure 104 having an outer surface and an inner surface defining oneor more fluid-flow passageways 106 configured to receive a cerebrospinalfluid of a biological subject. In an embodiment, the body structure 104includes a plurality of actuatable regions 1302 that are independentlyactuatable between at least a first transmissive state and a secondtransmissive state. In an embodiment, a sensor component 440 includingone or more sensors 442 configured to detect at least one characteristicassociated with a biological sample proximate at least one of the outersurface and the inner surface of the body structure 104. In anembodiment, the at least one characteristic associated with thebiological sample includes at least one of an autofluorescence, animmunofluorescence, or an indirect immunofluorescence. In an embodiment,the indwelling shunt apparatus includes one or more energy emitters 302configured to emit an energy stimulus based at least in part on at leastone detected characteristic associated with the biological sample.

In an embodiment, at least one of the plurality of actuatable regions1302 is energetically actuatable between an optically transparent stateand an optically reflective state. In an embodiment, at least one of theplurality of actuatable regions 1302 includes one or more activelycontrollable reflective or transmissive components. Non-limitingexamples of actively controllable reflective or transmissive componentsinclude liquid crystal components that are actively controllable betweena reflective state and a transmissive state, electrochromic componentsthat are actively controllable between a reflective state and atransmissive state, and the like.

In an embodiment, at least one of the plurality of actuatable regions1302 is controllably actuatable between an optically transparent stateand an optically reflective state. In an embodiment, at least one of theplurality of actuatable regions 1302 is actively controllable between atransmissive state and a reflective state. In an embodiment, at leastone of the plurality of actuatable regions 1302 is actively controllablebetween a transmissive state and a less transmissive state. In anembodiment, at least one of the plurality of actuatable regions 1302 isconfigured to outwardly transmit or internally reflect an energystimulus propagated through at least one of the one or more fluid-flowpassageways 106.

In an embodiment, the sensor component 440 is configured to detect atleast one of a characteristic of a cerebrospinal fluid received withinone or more fluid-flow passageways 106, a characteristic of a tissueproximate the one or more fluid-flow passageways 106, and aphysiological characteristic of the biological subject.

In an embodiment, the indwelling shunt includes a controller 402operably coupled to at least one of the plurality of actuatable regions,the controller 402 configured to cause an outward-transmission orinternal-reflection of an energy stimulus propagated through at leastone of the one or more fluid-flow passageways 106 based on detectedinformation from the sensor component 440.

In an embodiment, the sensor component 440 includes one or moreelectrochemical transducers, photochemical transducer, opticaltransducers, piezoelectrical transducers, or thermal transducers. In anembodiment, the sensor component 440 includes one or more thermaldetectors, photovoltaic detectors, or photomultiplier detectors. In anembodiment, the sensor component 440 includes one or more charge coupleddevices, complementary metal-oxide-semiconductor devices, photodiodeimage sensor devices, whispering gallery mode micro cavity devices, orscintillation detector devices. In an embodiment, the sensor component440 includes one or more ultrasonic transducers.

In an embodiment, the sensor component 440 includes one or more densitysensors. In an embodiment, the one or more density sensors include oneor more optical density sensors. In an embodiment, the one or moredensity sensors include one or more refractive index sensors. In anembodiment, the one or more refractive index sensors include one or morefiber optic refractive index sensors.

In an embodiment, the sensor component 440 includes one or more surfaceplasmon resonance sensors. In an embodiment, the sensor component 440includes one or more localized surface plasmon resonance sensors. In anembodiment, the sensor component 440 includes a light transmissivesupport and a reflective metal layer. In an embodiment, the sensorcomponent includes one or more acoustic biosensors, amperometricbiosensors, calorimetric biosensors, optical biosensors, orpotentiometric biosensors. In an embodiment, the sensor component 440includes one or more fluid flow sensors. In an embodiment, the sensorcomponent 440 includes one or more differential electrodes.

In an embodiment, the sensor component 440 includes one or morebiological mass sensors. In an embodiment, the sensor component 440includes one or more immuno sensors. In an embodiment, the sensorcomponent 440 includes one or more functionalized cantilevers. In anembodiment, the sensor component 440 includes a biological moleculecapture layer. In an embodiment, the sensor component 440 includesbiological molecule capture layer having an array of different bindingmolecules that specifically bind one or more target molecules. In anembodiment, the sensor component 440 includes a spectrometer (e.g., amass spectrometer, nuclear magnetic resonance spectrometer, UV-VISspectrometer, and the like).

In an embodiment, at least one of the one or more sensors 442 isconfigured to detect a fluorescence associated with an autofluorescentmaterial of biological sample proximate at least one of the outersurface and the inner surface of the body structure 104. In anembodiment, at least one of the one or more sensors 442 is configured todetect at least one of an emitted energy and a remitted energy, and togenerate a response based on the detected at least one of the emittedenergy or the remitted energy. In an embodiment, the indwelling shuntincludes one or more optical materials on at least a portion of a bodystructure 104 to internally reflect at least a portion of an emittedenergy stimulus from the one or more energy emitters 302 into aninterior of at least one of the one or more fluid-flow passageways 106.

In an embodiment, at least one of the one or more fluid-flow passageways106 includes a surface region 1304 that is energetically actuatablebetween an optically transparent state and an optically reflectivestate. In an embodiment, at least one of the one or more fluid-flowpassageways 106 includes one or more regions 1305 that are controllablyactuatable between an optically transparent state and an opticallyreflective state. In an embodiment, at least one of the one or morefluid-flow passageways 106 includes one or more regions 1308 that areactively controllable between a transmissive state and a reflectivestate. In an embodiment, at least one of the one or more fluid-flowpassageways 106 includes one or more regions 1310 that are activelycontrollable between a transmissive state and a less transmissive state.In an embodiment, at least one of the one or more fluid-flow passageways106 includes one or more liquid crystal components that are activelycontrollable between a transmissive state and a less transmissive state.In an embodiment, at least one of the one or more fluid-flow passageways106 includes one or more electrochromic components that are activelycontrollable between a transmissive state and a less transmissive state.

In an embodiment, the implantable device 102 includes a body structure104 having one or more actively controllable reflective or transmissivecomponents 1312 configured to outwardly transmit or internally reflectan energy stimulus propagated through at least one of the one or morefluid-flow passageways 106. The implantable device 102 can furtherinclude a sensor component 440 configured to detect at least one of acharacteristic of a cerebrospinal fluid received within one or morefluid-flow passageways 106, a characteristic of a tissue proximate theone or more fluid-flow passageways 106, and a physiologicalcharacteristic of the biological subject. The implantable device 102 canfurther include one or more actively controllable reflective ortransmissive components 1312 configured to outwardly transmit orinternally reflect an energy stimulus propagated through at least one ofthe one or more fluid-flow passageways 106. The implantable device 102can further include a controller 402 operably coupled to at least one ofthe one or more actively controllable reflective and transmissivecomponents 1312. In an embodiment, the controller 402 is configured tocause an outward-transmission or internal-reflection of an energystimulus propagated through at least one of the one or more fluid-flowpassageways 106 based on detected information from the sensor component440.

In an embodiment, a body structure 104 defining at least one of the oneor more fluid-flow passageways 106 includes a self-cleaning coatingcomposition. In an embodiment, the self-cleaning coating compositioncomprises an energy-activatable self-cleaning material. In anembodiment, the self-cleaning coating composition comprises a chemicallyactivatable self-cleaning material. In an embodiment, the self-cleaningcoating composition comprises one or more of titanium dioxide,superhydrophobic materials, or carbon nanotubes with nanoscopic paraffincoatings. In an embodiment, the self-cleaning coating compositioncomprises one or more of non-fouling zwitterionic polymers, zwitterionicsurface forming materials, zwitterionic polymers, poly(carboxybetainemethacrylate) (pCBMA), poly(carboxybetaine acrylic amide) (pCBAA),poly(oligo(ethylene glycol) methyl ether methacrylate) (pOEGMA),poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2′-(methacryloyloxy)ethyl]-ammoniumbromide), cationic pC8NMA, switchable pCBMA-1 C2, or pCBMA-2.

In an embodiment, the self-cleaning coating composition comprises one ormore antimicrobial agents. In an embodiment, at least one of the one ormore fluid-flow passageways 106 includes a coating configured togenerate a reactive oxygen specie or a reactive nitrogen specie whenexposed to an energy stimulus. In an embodiment, at least one of the oneor more fluid-flow passageways 106 includes a self-cleaning coatingconfigured to hydrolyze when exposed to an energy stimulus. In anembodiment, at least one of the one or more fluid-flow passageways 106includes a self-cleaning coating configured to degrade when exposed toan energy stimulus. In an embodiment, at least one of the one or morefluid-flow passageways 106 includes one or more reflective materials andone or more self-cleaning materials. In an embodiment, at least one ofthe one or more fluid-flow passageways 106 includes one or morereflective coatings and one or more self-cleaning coatings.

Referring to FIG. 13, in an embodiment, the implantable device 102includes a body structure 104 including one or more components 1302 thatare energetically actuatable among a plurality of wettability states. Itmay be possible to affect adhesion of, for example, bacteria and biofilmformation by changing the functional and chemical character of a surfaceon an implantable device 102. It may also be possible to modulate theadhesion and biofilm formation by modulating the functional and chemicalcharacter of a surface on an implantable device 102. By modulating thefunctional and chemical character of a surface on an implantable device102, it may also be possible to affect the transport properties of afluid exposed to the surface on an implantable device 102. Controllablewettability components can be made using a variety of methodologies andtechnologies including, for example, spray pyrolysis,electro-deposition, electro-deposition onto laser-drilled polymer molds,laser cutting and electro-polishing, laser micromachining, surfacemicro-machining, soft lithography, x-ray lithography, LIGA techniques(e.g., X-ray lithography, electroplating, and molding), conductive paintsilk screen techniques, conventional pattering techniques, injectionmolding, conventional silicon-based fabrication methods (e.g.,inductively coupled plasma etching, wet etching, isotropic andanisotropic etching, isotropic silicon etching, anisotropic siliconetching, anisotropic GaAs etching, deep reactive ion etching, siliconisotropic etching, silicon bulk micromachining, or the like),complementary-symmetry/metal-oxide semiconductor (CMOS) technology, deepx-ray exposure techniques, and the like. Further examples ofmethodologies and technologies for making controllable wettabilitycomponents can found in the following documents (the contents of whichare incorporated herein by reference): Feng et al., ReversibleSuper-hydrophobicity to Super-hydrophilicity Transition of Aligned ZnONanorod Films, J. Am. Chem. Soc., 126, 62-63 (2004), Lin et al.,Electrically Tunable Wettability of Liquid Crystal/Polymer CompositeFilms, Optics Express 16(22): 17591-598 (2008), Wang et al.,Photoresponsive Surfaces with Controllable Wettability, Journal ofPhotochemistry and Photobiology C: Photochemistry Reviews, 8(1): 18-29(2007), U.S. Pat. No. 6,914,279 (issued Jul. 5, 2005), and U.S. PatentPublication No. 2008/0223717 (published Sep. 18, 2008).

The wettability of a substrate can be determined using varioustechnologies and methodologies including contact angle methods, theGoniometer method, the Whilemy method, or the Sessile drop technique.Wetting is a process by which a liquid interacts with a solid.Wettability (the degree of wetting) is determined by a force balancebetween adhesive and cohesive force and is often characterized by acontact angle. The contact angle is the angle made by the intersectionof the liquid/solid interface and the liquid/air interface.Alternatively, it is the angle between a solid sample's surface and thetangent of a droplet's ovate shape at the edge of the droplet. Contactangle measurements provide a measure of interfacial energies and conveysdirect information regarding how hydrophilic or hydrophobic a surfaceis. For example, superhydrophilic surfaces have contact angles less thanabout 5°, hydrophilic surfaces have contact angles less than about 90°,hydrophobic surfaces have contact angles greater than about 90°, andsuperhydrophobic surfaces have contact angles greater than about 150°.

In an embodiment, the implantable device 102 includes a body structure104 including one or more components 1302 having switchable wettingproperties. In an embodiment, the implantable device 102 includes a bodystructure 104 including one or more components 1302 that areenergetically actuatable between at least a first wettability and asecond wettability. In an embodiment, the one or more components 1302are acoustically, chemically, electro-chemically, electrically,optically, thermally, or photo-chemically actuatable between at least afirst wettability and a second wettability.

In an embodiment, the one or more components 1302 include at least onephoto-responsive material. Non-limiting examples of photo-responsivematerials include SnO, SnO₂, TiO₂, W₂O₃, ZnO, ZnO, and the like. In anembodiment, the one or more components 1302 include at least one film,coating, or material including SnO, SnO₂, TiO₂, W₂O₃, ZnO, ZnO, or thelike. In an embodiment, the one or more components 1302 areUV-manipulatable between at least a first wettability and a secondwettability. In an embodiment, the one or more components 1302 includeone or more ZnO nano-rod films, coatings, or materials that areUV-manipulatable between a superhydrophobic state and superhydrophilicstate. In an embodiment, the one or more components 1302 include atleast one electrochemically active material. Non-limiting examples ofelectrochemically active materials include electrochemically activepolymers (e.g., polyaniline, polyethylenethioxythiophene, conjugatedpolymer poly(3-hexylthiophene), or the like), and the like.

In an embodiment, the one or more components 1302 include one or moresuperhydrophobic conducting polypyrrole films, coatings, or componentsthat are electrically switchable between an oxidized state and a neutralstate, resulting in reversibly switchable superhydrophobic andsuperhydrophilic properties. See, e.g., Lahann et al., A ReversiblySwitching Surface, 299 (5605): 371-374 (2003) 21:47-51 (2003), thecontents of which are incorporated herein by reference). In anembodiment, the one or more components 1302 include one or moreelectrically isolatable fluid-support structures. See, e.g., U.S. Pat.No. 7,535,692 (issued May 19, 2009), the contents of which areincorporated herein by reference). In an embodiment, the one or morecomponents 1302 include a plurality of volume-tunable nanostructures.See, e.g., U.S. Patent Publication No. 2008/0095977 (published Apr. 24,2008), the contents of which are incorporated herein by reference). Inan embodiment, the one or more components 1302 include one or moretunable (electrically tunable) superhydrophobic conducting polypyrrolefilms, coatings, or components. See, e.g., Krupenki et al, ElectricallyTunable Superhydrophobic Nanostructured Surfaces, Bell Labs TechnicalJournal 10 (3): 161-170 (2009), the contents of which are incorporatedherein by reference). In an embodiment, the one or more components 1302include one or more electrically tunable crystal/polymer composites. Inan embodiment, the one or more components 1302 include a switchablesurface. See e.g., Gras et al., Intelligent Control of SurfaceHydrophobicity, ChemPhysChem 8(14): 2036-2050 (2007).

In an embodiment, at least one of the one or more fluid-flow passageways106 includes one or more surface regions 1304 that are energeticallyactuatable between a substantially hydrophobic state and a substantiallyhydrophilic state. In an embodiment, at least one of the one or morefluid-flow passageways 106 includes a surface region 1304 that isenergetically actuatable between at least a first hydrophilic state anda second hydrophilic state. In an embodiment, at least one of the one ormore fluid-flow passageways 106 includes a surface region 1304 that isenergetically actuatable between a hydrophobic state and a hydrophilicstate. In an embodiment, at least one of the one or more fluid-flowpassageways 106 includes a surface region 1304 having a material that isswitchable between a zwitterionic state and a non-zwitterionic state. Inan embodiment, at least one of the one or more fluid-flow passageways106 includes at least one of an antimicrobial coating 1306 and anon-fouling coating 1308. In an embodiment, at least one of the one ormore fluid-flow passageways 106 includes an antimicrobial 1306 and anon-fouling coating 1308. In an embodiment, at least one of the one ormore fluid-flow passageways 106 includes a surface region 1304 that isenergetically actuatable between an antimicrobial state and anon-fouling state.

Referring to FIG. 14, in an embodiment, an implantable fluid managementdevice 1400 includes a catheter assembly 1402 defining one or morefluid-flow passageways 106 configured to receive a biological fluid of asubject. The catheter assembly 1402 can include, but is not limited to,a proximal portion 1404, a distal portion 1406, and one or more tubularstructures 1408 including an inflow fluid-flow passageway 1410 and anoutflow fluid-flow passageway 1412. In an embodiment, the inflowfluid-flow passageway 1410 is configured in fluid communication to oneor more inflow ports 1414, and the outflow fluid-flow passageway 1412 isconfigured in fluid communication to one or more outflow ports 1416

In an embodiment, an implantable fluid management device 1400 includesan actively controllable excitation component 910 configured toindependently deliver, in vivo, at least one of a first sterilizingenergy stimulus to a biological fluid received within at least one ofthe one or more fluid-flow passageways 106 and a second sterilizingenergy stimulus to a tissue proximate an outer surface of theimplantable fluid management device. In an embodiment, the activelycontrollable excitation component 910 is configured to concurrently orsequentially deliver the first sterilizing energy stimulus to abiological fluid received within at least one of the one or morefluid-flow passageways 106 and the second sterilizing energy stimulus toa region proximate an outer surface of the implantable fluid managementdevice 1400. In an embodiment, the first sterilizing energy stimulus orthe second sterilizing energy stimulus comprises an electromagneticstimulus, an electrical stimulus, an ultrasonic stimulus, or a thermalstimulus. In an embodiment, the first sterilizing energy stimuluscomprises one of an electrical sterilizing energy stimulus, anelectromagnetic sterilizing energy stimulus, an ultrasonic sterilizingenergy stimulus, or a thermal sterilizing energy stimulus, and thesecond sterilizing energy stimulus comprises a different one of anelectrical sterilizing energy stimulus, an electromagnetic sterilizingenergy stimulus, an ultrasonic sterilizing energy stimulus, or a thermalsterilizing energy stimulus. In an embodiment, the actively controllableexcitation component 910 is configured to concurrently or sequentiallydeliver at least a first energy stimulus and a second energy stimulus,the second energy stimulus different from the first energy stimulus. Inan embodiment, the first energy stimulus comprises one of anelectromagnetic energy stimulus, an electrical energy stimulus, anultrasonic energy stimulus, or a thermal energy stimulus, and the secondenergy stimulus comprises a different one of an electromagnetic energystimulus, an electrical energy stimulus, an ultrasonic energy stimulus,or a thermal energy stimulus.

In an embodiment, the implantable fluid management device 1400 isconfigured to provide an illumination pattern to a biological fluidreceived within at least one of the one or more fluid-flow passageways106, the illumination pattern comprising at least a first region and asecond region, the second region having at least one of an illuminationintensity, an energy-emitting pattern, a peak emission wavelength, anON-pulse duration, an OFF-pulse duration, and a pulse frequencydifferent from the first region. In an embodiment, the implantable fluidmanagement device 1400 is configured to provide an illumination patternto a tissue proximate a surface of the implantable fluid managementdevice implantable fluid management device 1400. In an embodiment, theactively controllable excitation component 910 is configured to providean illumination pattern to a biological fluid received within at leastone of the one or more fluid-flow passageways 106. In an embodiment, theillumination pattern includes at least a first region and a secondregion, the second region having at least one of an illuminationintensity, an energy-emitting pattern, a peak emission wavelength, anON-pulse duration, an OFF-pulse duration, and a pulse frequencydifferent from the first region. In an embodiment, the activelycontrollable excitation component 910 is configured to provide anillumination pattern to a tissue or biological fluid proximate a surfaceof the implantable fluid management device 1400.

In an embodiment, an implantable fluid management device 1400 includes afirst actively controllable excitation component 910 configured todeliver, in vivo, a first sterilizing energy stimulus to a biologicalfluid received within at least one of the one or more fluid-flowpassageways 106, and a second actively controllable excitation component910 a configured to deliver, in vivo, a second sterilizing energystimulus to a tissue proximate an outer surface of the implantable fluidmanagement device 1400. In an embodiment, an implantable fluidmanagement device 1400 includes a control means 1000 operably coupled toat least one of the first actively controllable excitation component 910and the actively controllable excitation component 910 a. In anembodiment, the implantable fluid management device 1400 is configuredto concurrently or sequentially deliver the first sterilizing energystimulus to a biological fluid received within at least one of the oneor more fluid-flow passageways 106 and the second sterilizing energystimulus to a tissue proximate an outer surface of the implantable fluidmanagement device 1400. In an embodiment, the first sterilizing energystimulus or the second sterilizing energy stimulus comprises anelectromagnetic stimulus, an electrical stimulus, an ultrasonicstimulus, or a thermal stimulus. In an embodiment, the first sterilizingenergy stimulus comprises one of an electrical sterilizing energystimulus, an electromagnetic sterilizing energy stimulus, an ultrasonicsterilizing energy stimulus, or a thermal sterilizing energy stimulus,and the second sterilizing energy stimulus comprises a different one ofan electrical sterilizing energy stimulus, an electromagneticsterilizing energy stimulus, an ultrasonic sterilizing energy stimulus,or a thermal sterilizing energy stimulus. In an embodiment, theimplantable fluid management device 1400 is configured to concurrentlyor sequentially deliver at least a first energy stimulus and a secondenergy stimulus, the second energy stimulus different from the firstenergy stimulus. In an embodiment, the first energy stimulus comprisesone of an electromagnetic energy stimulus, an electrical energystimulus, an ultrasonic energy stimulus, or a thermal energy stimulus,and the second energy stimulus comprises a different one of anelectromagnetic energy stimulus, an electrical energy stimulus, anultrasonic energy stimulus, or a thermal energy stimulus.

FIG. 15 shows an example of an in vivo method 1500 of treating aninfectious agent. At 1510, the method 1500 includes providing an energystimulus for a time and amount sufficient to induce PCD of an infectiousagent within a cerebrospinal fluid of a mammal, the cerebrospinal fluidreceived within one or more fluid-flow passageways 106 of an indwellingimplant including one or more energy-emitting components 902energetically coupleable to an interior of the one or more fluid-flowpassageways 106. At 1512, providing the sufficient amount of the energystimulus includes providing a sufficient amount of at least one of anx-ray, ultraviolet, visible, infrared, near infrared, terahertz,microwave, and radio frequency radiation. At 1514, providing thesufficient amount of the energy stimulus includes delivering aneffective dose of optical energy at which a cell preferentiallyundergoes PCD compared to necrosis. At 1516, providing the sufficientamount of the energy stimulus includes providing an ultravioletradiation of a character or duration to induce cell death by PCD. At1518, providing the sufficient amount of the energy stimulus includesproviding a dose of an ultraviolet radiation based on a detectedcharacteristic associated with the cerebrospinal fluid. At 1520,providing the sufficient amount of the energy stimulus includesproviding an electromagnetic energy stimulus of a character and for asufficient time to induce PCD without substantially inducing necrosis ofan infectious agent present in the cerebrospinal fluid.

At 1530, the method 1500 can further include delivering an active agentcomposition (e.g., an antimicrobial agent composition, or the like) to acerebrospinal fluid received within at least one of the one or morefluid-flow passageways 106. At 1532, delivering an active agentcomposition includes delivering an active agent composition (e.g., anantimicrobial agent composition, or the like) to a cerebrospinal fluidreceived within at least one of the one or more fluid-flow passageways106. At 1540, the method 1500 can further include delivering anantimicrobial agent composition to a cerebrospinal fluid received withinat least one of the one or more fluid-flow passageways 106 at a dosesufficient to attenuate an activity of the infectious agent. At 1542,delivering an active agent composition includes delivering anantimicrobial agent composition to a cerebrospinal fluid received withinat least one of the one or more fluid-flow passageways 106 at a dosesufficient to attenuate an activity of the infectious agent

FIG. 16 shows an example of a method 1600 inhibiting a microbialcolonization in the cerebrospinal fluid of a biological subject. At1610, the method 1600 includes selectively energizing one or moreregions of at least one fluid-flow passageway 106 of an indwellingimplant cerebrospinal fluid management system via one or moreenergy-emitting components 902 in optical communication with an interiorof the least one fluid-flow passageway 106. At 1612, selectivelyenergizing includes energetically interrogating a cerebrospinal fluidreceived within the one or more regions of the at least one fluid-flowpassageway 106 with an energy stimulus having a peak emission wavelengthranging from about 100 nanometers to about 400 nanometers. At 1614,selectively energizing includes energetically interrogating acerebrospinal fluid received within the one or more regions of the atleast one fluid-flow passageway 106 with an energy stimulus having apeak emission wavelength ranging from about 100 nanometers to about 320nanometers. At 1616, selectively energizing includes energeticallyinterrogating a cerebrospinal fluid received within the one or moreregions of the at least one fluid-flow passageway 106 with an energystimulus having a peak emission wavelength ranging from about 280nanometers to about 320 nanometers. At 1618, selectively energizingincludes energizing a cerebrospinal fluid received within the one ormore regions of the at least one fluid-flow passageway 106 with anenergy stimulus having an operational fluence of the one or more energyemitters 302 is less than about 80 milli-joules per square centimeter.At 1620, selectively energizing includes energizing a cerebrospinalfluid received within the one or more regions of the at least onefluid-flow passageway 106 with an energy stimulus having an operationalfluence of less than about 35 milli-joules per square centimeter. At1622, selectively energizing includes energizing a cerebrospinal fluidreceived within the one or more regions of the at least one fluid-flowpassageway 106 with an energy stimulus having an operational fluence ofless than about 15 milli-joules per square centimeter. At 1624,selectively energizing includes energizing a cerebrospinal fluidreceived within the one or more regions of the at least one fluid-flowpassageway 106 with an energy stimulus having an average energy densityranging from about less than about 15 milli-joules per square centimeterto about less than about 80 milli-joules per square centimeter.

At 1630, the method 1600 includes delivering an active agent compositionto an interior of at least one fluid-flow passageway of an indwellingimplant cerebrospinal fluid management system via one or more activeagent assemblies in fluidic communication with the interior of the leastone fluid-flow passageway.

FIG. 17 shows an example of a method 1700. At 1710, the method 1700includes selectively energizing one or more regions of at least onefluid-flow passageway 106 of an in vivo implanted cerebrospinal fluidmanagement system in response to an automatically detected opticaldensity parameter associated with a cerebrospinal fluid received withinthe at least one fluid-flow passageway 106. At 1712, selectivelyenergizing one or more regions of the at least one fluid-flow passageway106 includes delivering at least one of an electromagnetic energystimulus, an electrical energy stimulus, an ultrasonic energy stimulus,and a thermal energy stimulus in response to the automatically detectedoptical density parameter associated with the cerebrospinal fluidreceived within the at least one fluid-flow passageway 106. At 1714,selectively energizing one or more regions of the at least onefluid-flow passageway 106 includes concurrently or sequentiallydelivering at least a first energy stimulus to a first region and asecond energy stimulus to a second region. At 1716, selectivelyenergizing one or more regions of the at least one fluid-flow passageway106 includes concurrently or sequentially delivering a first energystimulus to at least a first region and a second energy stimulus to atleast a second region, the first energy stimulus comprising one of anelectromagnetic energy stimulus, an electrical energy stimulus, anultrasonic energy stimulus, or a thermal energy stimulus, and the secondenergy stimulus comprising a different one of an electromagnetic energystimulus, an electrical energy stimulus, an ultrasonic energy stimulus,or a thermal energy stimulus.

At 1720, the method 1700 includes delivering an active agent compositionto one or more regions of at least one fluid-flow passageway of an invivo implanted cerebrospinal fluid management system in response to anautomatically detected optical density parameter associated with acerebrospinal fluid received within the at least one fluid-flowpassageway.

FIG. 18 shows an example of a method 1800. At 1810, the method 1800includes providing an energy stimulus to an interior of one or morefluid-flow passageways 106 of an in vivo implanted cerebrospinal fluidmanagement device in response to a change in a refractive indexparameter associated with a cerebrospinal fluid received within the atleast one fluid-flow passageway 106. At 1812, providing the energystimulus includes providing a spatially patterned energy stimulus havingat least a first region and a second region different from the firstregion. In an embodiment, the first regions comprises one of a spatiallypatterned electromagnetic energy stimulus, a spatially patternedelectrical energy stimulus, a spatially patterned ultrasonic energystimulus, or a spatially patterned thermal energy stimulus, and thesecond region comprises a different one of a spatially patternedelectromagnetic energy stimulus, a spatially patterned electrical energystimulus, a spatially patterned ultrasonic energy stimulus, or aspatially patterned thermal energy stimulus. At 1814, providing theenergy stimulus includes providing an illumination pattern comprising atleast a first region and a second region, the second region having atleast one of an illumination intensity, an energy-emitting pattern, apeak emission wavelength, an ON-pulse duration, an OFF-pulse duration,and a pulse frequency different from the first region. At 1816,providing the energy stimulus includes providing a voltage to acerebrospinal fluid received within at least one of the one or morefluid-flow passageways 106, the voltage of sufficient strength orduration to exceed a nominal dielectric strength of a cell plasmamembrane. At 1818, providing the energy stimulus includes concurrentlyor sequentially providing at least a first energy stimulus and a secondenergy stimulus the second energy stimulus different from the firstenergy stimulus. In an embodiment, the first energy stimulus comprisesone of an electromagnetic energy stimulus, an electrical energystimulus, an ultrasonic energy stimulus, or a thermal energy stimulus,and the second energy stimulus comprises a different one of anelectromagnetic energy stimulus, an electrical energy stimulus, anultrasonic energy stimulus, or a thermal energy stimulus.

At 1820, the method 1800 can further include providing an energystimulus to a tissue proximate an outer surface of the implantable fluidmanagement device. At 1822, providing the energy stimulus includesindependently delivering, in vivo, at least one of a first sterilizingenergy stimulus to the biological fluid received within at least one ofthe one or more fluid-flow passageways 106 and a second sterilizingenergy stimulus to the tissue proximate an outer surface of theimplantable fluid management device. At 1824, providing the energystimulus includes independently delivering, in vivo, at least one of afirst sterilizing energy stimulus to the biological fluid receivedwithin at least one of the one or more fluid-flow passageways 106 and asecond sterilizing energy stimulus to the tissue proximate an outersurface of the implantable fluid management device based at least inpart on a detected change in a refractive index parameter associatedwith the cerebrospinal fluid.

FIG. 19 shows an example of a method 1900. At 1910, the method 1900includes delivering one or more energy stimuli to at least one of aninterior and an exterior of one or more fluid-flow passageways 106 of anindwelling cerebrospinal fluid management apparatus in response to an invivo detected change in a refractive index parameter associated with acerebrospinal fluid received within the one or more fluid-flowpassageways 106. At 1912, delivering the one or more energy stimuliincludes directing a first portion of an emitted energy stimulus along asubstantially lateral direction in the interior of at least one of theone or more fluid-flow passageways 106 and directing a second portion ofthe emitted energy stimulus along a substantially longitudinal directionin the interior of at least one of the one or more fluid-flowpassageways 106. At 1914, delivering the one or more energy stimuliincludes directing at least a first portion of an emitted one or moreenergy stimuli, via a first optical component, along a substantiallylateral direction in a first region of at least one of the one or morefluid-flow passageways 106 and directing at a second portion of theemitted energy stimulus, via a second optical component, along asubstantially lateral direction in a second region of the one or morefluid-flow passageways 106, the second region different from the firstregion. At 1916, delivering the one or more energy stimuli includesdirecting a portion of an emitted energy stimulus along a substantiallylongitudinal direction in a first region of at least one of the one ormore fluid-flow passageways 106 and directing a portion of the emittedenergy stimulus along a substantially longitudinal direction in a secondregion of the one or more fluid-flow passageways 106, the second regiondifferent from the first region. At 1918, delivering the one or moreenergy stimuli includes directing at least a portion of an emittedenergy stimulus along a substantially lateral direction in a firstregion of at least one of the one or more fluid-flow passageways 106 anddirecting at least a portion of the emitted energy stimulus along asubstantially lateral direction in a second region of the one or morefluid-flow passageways 106, the second region different from the firstregion.

FIG. 20 shows an example of a method 2000. At 2010, the method 2000includes concurrently or sequentially delivering two or more energystimuli to an interior and an exterior of one or more fluid-flowpassageways 106 of an indwelling cerebrospinal fluid managementapparatus in response to a detected parameter associated with one ormore of a cerebrospinal fluid received within the one or more fluid-flowpassageways 106, a detected parameter associated with a tissue proximatean outer surface of the one or more fluid-flow passageways 106, or acharacteristic associated with a biological subject. At 2012,concurrently or sequentially delivering the two or more energy stimuliincludes concurrently or sequentially delivering at least a first energystimulus and a second energy stimulus, the second energy stimulusdifferent from the first energy stimulus. In an embodiment, the firstenergy stimulus comprises one of an electromagnetic energy stimulus, anelectrical energy stimulus, an ultrasonic energy stimulus, or a thermalenergy stimulus, and the second energy stimulus comprises a differentone of an electromagnetic energy stimulus, an electrical energystimulus, an ultrasonic energy stimulus, or a thermal energy stimulus.At 2014, concurrently or sequentially delivering the two or more energystimuli includes concurrently or sequentially delivering a firstelectrical stimulus and a second electrical stimulus, in vivo, to targettissue proximate the implanted or inserted surgical implant, the firstelectrical stimulus or the second electrical stimulus of a character orduration to inhibit scar formation, and the other of the firstelectrical stimulus or the second electrical stimulus of a character orduration to promote growth of tissue. At 2016, concurrently orsequentially delivering the two or more energy stimuli includesconcurrently or sequentially delivering the first sterilizing energystimulus to a biological fluid received within at least one of the oneor more fluid-flow passageways 106 and the second sterilizing energystimulus to a tissue proximate an outer surface of the indwellingcerebrospinal fluid management apparatus.

FIG. 21 shows an example of a method 2100. At 2110, the method 2100includes comparing, via integrated circuitry, one or morecharacteristics communicated from an implanted shunt device to storedreference data, the one or more characteristics including at least oneof information associated with a cerebrospinal fluid received within oneor more fluid-flow passageways 106 of the implanted shunt device,information associated with a tissue proximate an outer surface of theimplanted shunt device, and information associated with a physiologicalcharacteristic of the biological subject. At 2120, the method 2100includes initiating a treatment protocol based at least in part on thecomparison. At 2122, initiating the treatment protocol includesselectively energizing one or more regions proximate a surface of theimplanted shunt device via one or more energy-emitters based at least inpart on the comparison. At 2124, initiating the treatment protocolincludes delivering an active agent composition to one or more regionsproximate a surface of the implanted shunt device via one or more activeagent assemblies based at least in part on the comparison. At 2126,initiating the treatment protocol includes activating an authorizationprotocol, activating an authentication protocol, activating an energystimulus protocol, activating an active agent delivery protocol, oractivating an infection sterilization diagnostic protocol based at leastin part on the comparison.

FIG. 22 shows an example of a method 2200. At 2210, the method 2200includes sending information to an implantable device 102, prior,during, or after delivery of an energy stimulus, in vivo, to tissue orbiological fluid proximate a surface of the implantable device 102. Inan embodiment, sending information to an implantable device 102 includessending information to an implantable device 102, prior, during, orafter delivery of at least one of an electrical sterilizing stimulus, anelectromagnetic sterilizing stimulus, an ultrasonic sterilizingstimulus, and a thermal sterilizing stimulus. At 2220, the method 2200includes generating a response based on the sent information. At 2222,generating the response can include at least one of generating aresponse signal, activating a computer-implemented method, activating aninteractive user interface, and activating a display. At 2224,generating the response can include at least one of activating anauthorization protocol display, activating an authentication protocoldisplay, activating a software update protocol display, activating adata transfer protocol display, and activating an infectionsterilization diagnostic protocol display.

FIG. 23 shows an example of a method 2300. At 2310, the method 2300includes sending information to an implantable device that includes: oneor more fluid-flow passageways 106, an actively controllable excitationcomponent 910 configured to deliver an electrical sterilizing stimulus,in vivo, to tissue or a biological fluid proximate a surface of theimplantable device 102, and a controller 402 communicatively coupled tothe actively controllable excitation component 910. At 2312, sendinginformation can include sending at least one of a command, software,data, and a code. At 2314, sending information can include sendinginformation associated with at least one of an authentication protocol,an authorization protocol, a delivery protocol, an activation protocol,an encryption protocol, and a decryption protocol. In an embodiment,sending information includes sending information associated with atleast one of an electrical sterilizing stimulus delivery protocol, anelectromagnetic sterilizing stimulus delivery protocol, an ultrasonicsterilizing stimulus delivery protocol, and a thermal sterilizingstimulus delivery protocol. At 2316, sending information includessending at least one of an authorization instruction, an authenticationinstruction, a prescription dosing instruction, a sterilizing stimulusadministration instruction, and a prescribed regimen instruction. At2318, sending information includes sending at least one of aninstruction stream, an encrypted data stream, an authentication datastream, and an authorization data stream. At 2320, sending informationincludes sending at least one of an activation code, an error code, acommand code, and an authorization code. In an embodiment, sendinginformation includes sending at least one of patient information, sensorinformation, detected data, physiological sensor data, and physiologicalreference data. At 2322, sending information includes sending at leastone of a sterilizing stimulus delivery regimen parameter, a temporalsterilizing energy stimulus delivery pattern parameter, a spaced-apartsterilizing stimulus delivery pattern parameter, a spatial electricfield modulation parameter, a spatial electric field magnitudeparameter, a spatial electric field distribution parameter, an ON-rate,and an OFF-rate. At 2324, sending information includes sendinginformation associated with at least one of an active agent deliverypattern parameter, an active agent delivery regimen parameter, and anactive agent delivery rate parameter. In an embodiment, sendinginformation includes sending information associated with at least one ofan electrical sterilizing stimulus delivery pattern parameter, anelectromagnetic sterilizing stimulus delivery pattern parameter, anultrasonic sterilizing stimulus delivery pattern parameter, and athermal sterilizing stimulus delivery pattern parameter. In anembodiment, sending information includes sending information associatedwith at least one of an electrical sterilizing stimulus delivery regimenparameter, an electromagnetic sterilizing stimulus delivery regimenparameter, an ultrasonic sterilizing stimulus delivery regimenparameter, and a thermal sterilizing stimulus delivery regimenparameter.

At 2330, the method 2300 includes receiving information from theimplantable device 102. At 2332, receiving information from theimplantable device 102 includes receiving implantable deviceinformation, patient information, user information, sterilizing stimulusdelivery information, stored information, sterilization regimeninformation, regulatory compliance information, sensor information, orimplantable device use information. At 2334, receiving information fromthe implantable device 102 includes receiving regulatory complianceinformation or regulatory use information. In an embodiment, receivinginformation includes receiving sensor data. In an embodiment, receivinginformation includes receiving a control signal. In an embodiment,receiving information includes receiving a request for transmission ofinformation. In an embodiment, receiving information includes receivinga request for transmission of at least one of data, a command, anauthorization, an update, and a code.

FIG. 24 shows an example of a method 2400. At 2410, the method 2400includes sending a first information stream to an implantable device102. At 2412, sending the first information stream includes sendinginformation associated with at least one of an active agent deliverypattern parameter, an active agent delivery regimen parameter, and anactive agent delivery rate parameter. At 2414, sending the firstinformation stream includes sending information associated with at leastone of a cryptographic protocol, a decryption protocol, an encryptionprotocol, a regulatory compliance protocol, and regulatory use protocol.At 2420, the method 2400 includes sending a second information stream tothe implantable device 102 based on a response to the sent firstinformation stream. At 2422, sending the second information streamincludes sending information associated with at least one of an activeagent delivery pattern parameter, an active agent delivery regimenparameter, and an active agent delivery rate parameter. At 2424, sendingthe second information stream includes sending information associatedwith at least one of a cryptographic protocol, a decryption protocol, anencryption protocol, a regulatory compliance protocol, and regulatoryuse protocol. At 2426, sending the second information stream includessending information associated with at least one of a sterilizing energystimulus delivery regimen parameter, a spaced-apart sterilizing energystimulus delivery pattern parameter, a spatial electric field modulationparameter, a spatial electric field magnitude parameter, and a spatialelectric field distribution parameter.

FIG. 25 shows an example of a method 2500. At 2510, the method 2500includes receiving information from an implantable device 102 thatincludes: one or more fluid-flow passageways 106, an activelycontrollable excitation component 910 configured to deliver asterilizing energy stimulus, in vivo, to tissue or a biological fluidproximate a surface of the implantable device 102, and a controller 402communicatively coupled to the actively controllable excitationcomponent. At 2512, receiving information includes receiving at leastone of a command, an update, data, and a code. At 2514, receivinginformation includes receiving information associated with at least oneof an illumination pattern an excitation intensity, an excitationfrequency, an excitation pulse frequency, an excitation pulse ratio, anexcitation pulse intensity, an excitation pulse duration time, anexcitation pulse repetition rate, an ON-rate, and an OFF-rate. At 2516,receiving information includes receiving information associated with anelectrical sterilizing stimulus delivery regimen. At 2518, receivinginformation includes receiving information associated with at least oneof a spaced-apart electrical sterilizing stimulus delivery patternparameter, a spatial electric field modulation parameter, a spatialelectric field magnitude parameter, and a spatial electric fielddistribution parameter. In an embodiment, receiving information includesreceiving sensor data. In an embodiment, receiving information includesreceiving a control signal. In an embodiment, receiving informationincludes receiving a request for transmission of information. In anembodiment, receiving information includes receiving a request fortransmission of at least one of data, a command, an authorization, anupdate, and a code.

At 2520, the method 2500 includes generating a response based on thereceived information. At 2522, generating the response includesgenerating at least one of a response signal, an authenticationresponse, and an authorization response. At 2524, generating theresponse includes at least one of storing at least one parameterassociated with the received information, storing at least a portion ofthe received information, and decrypting at least a portion of thereceived information. At 2526, generating the response includes at leastone of initiating a cryptographic protocol, initiating a decryptionprotocol, and initiating an encryption protocol. In an embodiment,generating the response includes generating at least one of a controlsignal, data, a command, an authorization, an update, and a code.

FIGS. 26A and 26B show an example of a method 2600. At 2610, the method2600 includes providing one or more parameters associated with theactively controlled delivery of a sterilizing energy stimulus to animplantable device 102. In an embodiment, providing the one or moreparameters includes providing information to the implantable device 102,the information associated with the actively controlled delivery of atleast one of an electrical sterilizing stimulus, an electromagneticsterilizing stimulus, an ultrasonic sterilizing stimulus, and a thermalsterilizing stimulus, in vivo, to tissue or a biological fluid proximatethe implantable device 102. In an embodiment, providing the one or moreparameters includes providing information associated with the activelycontrolled delivery of an electrical stimulus, in vivo, to tissue or abiological fluid proximate a surface of the implantable device 102. At2612, providing the one or more parameters includes providinginformation associated with the actively controlled delivery of anelectromagnetic stimulus, in vivo, to tissue proximate a first outersurface of the implantable device 102. At 2614, providing the one ormore parameters includes providing information associated with at leastone of an illumination pattern an excitation intensity, an excitationfrequency, an excitation pulse frequency, an excitation pulse ratio, anexcitation pulse intensity, an excitation pulse duration time, anexcitation pulse repetition rate, an ON-rate, and an OFF-rate. At 2616,providing the one or more parameters includes providing one or moreparameters associated with an electrical sterilizing stimulus deliveryregimen. At 2618, providing the one or more parameters includesproviding one or more parameters associated with at least one of aspaced-apart electrical sterilizing stimulus delivery pattern parameter,a spatial electric field modulation parameter, a spatial electric fieldmagnitude parameter, and a spatial electric field distributionparameter. In an embodiment, providing the one or more parametersincludes providing information associated with the actively controlleddelivery of an ultrasonic stimulus, in vivo, to tissue proximate a firstouter surface of the implantable device. In an embodiment, providing theone or more parameters includes providing information associated withthe actively controlled delivery of a thermal stimulus, in vivo, totissue proximate a first outer surface of the implantable device. In anembodiment, providing the one or more parameters includes providinginformation associated with a spatial-pattern of the sterilizing energystimulus. In an embodiment, providing the one or more parametersincludes providing information associated with a spatial-patterndistribution of the sterilizing energy stimulus. In an embodiment,providing the one or more parameters includes providing informationassociated with a temporal-pattern of the sterilizing energy stimulus.In an embodiment, providing the one or more parameters includesproviding the one or more parameters based at least in part on obtainedinformation.

At 2620 the method 2600 includes providing information to theimplantable device 102 based on a generated response to the provided oneor more parameters. In an embodiment, providing the one or moreparameters includes providing the one or more parameters based at leastin part on obtained information. In an embodiment, providing the one ormore parameters includes providing the one or more parameters inresponse to the obtained information. At 2630, the method 2600 includesobtaining information associated with the at least one physiologicalcharacteristic associated with a biological subject from the implantabledevice 102. At 2632, obtaining information includes obtaining one ormore parameters associated with at least one of a temperature, animpedance, a sodium level, a density, a glucose level, a lipoproteinlevel, a cholesterol level, a triglyceride level, a hormone level, ablood oxygen level, a pulse rate, a blood pressure, an intracranialpressure, and a respiratory rate associated with the biological subject.At 2634, obtaining information includes obtaining one or morehematological parameters. At 2636, obtaining information includesobtaining one or more hematological parameters associated with ahematological abnormality. At 2638, obtaining information includesobtaining one or more parameters associated with at least one ofleukopenia, leukophilia, lymphocytopenia, lymphocytophilia, neutropenia,neutrophilia, thrombocytopenia, disseminated intravascular coagulation,bacteremia, and viremia. At 2640, obtaining information includesobtaining one or more parameters associated with at least one of aninfection marker, an inflammation marker, an infective stress marker, asystemic inflammatory response syndrome marker, and a sepsis marker. At2642, obtaining information includes obtaining one or more parametersassociated with at least one of a red blood cell count, a lymphocytelevel, a leukocyte count, a myeloid count, an erythrocyte sedimentationrate, and a change to C-reactive protein level. At 2644, obtaininginformation includes obtaining one or more parameters associated with atleast one of a cytokine plasma concentration and an acute phase proteinplasma concentration. At 2646, obtaining information includes obtainingone or more parameters associated with at least one of an infectionindicator, an inflammation indicator, an infective stress indicator, anda sepsis indicator. At 2648, obtaining information includes obtainingone or more parameters associated with at least one of an infection, aninflammation, an infective stress, or a sepsis. In an embodiment,obtaining information includes obtaining one or more parametersassociated with at least one of an infection, an inflammation, aninfective stress, and a sepsis.

FIG. 27 shows an example of a method 2700. At 2710, the method 2700includes providing a first information to an implantable device 102. At2720, the method 2700 includes obtaining a second information from theimplant based on a response to the first information. At 2730, themethod 2700 includes providing information to the implantable device 102based on the second information.

FIG. 28 shows an example of a method 2800. At 2810, the method 2800includes receiving information from an implantable device 102, duringdelivery of a sterilizing energy stimulus, in vivo, to tissue orbiological fluid proximate a surface of the implantable device 102. At2820, the method 1600 includes generating a response based on thereceived information.

FIG. 29 shows an example of a method 2900. At 2910, the method 2900includes receiving information from an implantable device 102, afterdelivery of a sterilizing energy stimulus, in vivo, to tissue or abiological fluid proximate the implantable device 102. At 2920, themethod 2900 includes generating a response based on the receivedinformation.

FIG. 30 shows an example of a method 3000. At 3010, the method 3000includes receiving information from an implantable device 102, beforedelivery of a sterilizing energy stimulus, in vivo, to a biologicalfluid or tissue proximate an inner or an outer surface of theimplantable device 102. At 3020, the method 3000 includes generating aresponse based on the received information. At 3022, generating theresponse includes activating a third-party device. At 3024, generatingthe response includes activating an authorization protocol. At 3026,generating the response includes activating an authentication protocol.At 3028, generating the response includes activating a software updateprotocol. At 3030, generating the response includes activating a datatransfer protocol. At 3032, generating the response includes activatingan infection sterilization diagnostic protocol.

FIG. 31 shows an example of a method 3100 of treating scar formationpost surgery. Following an injury to a tissue, localized release ofinflammatory mediators may occur as a result of damaged endothelialcells and platelet aggregation at the site of injury. This inflammatoryresponse is a normal part of the wound repair process, preventinginfection and promoting fibrosis and wound closure. Inflammatorymediators such as transforming growth factor (TGF) β family,platelet-derived growth factors (PDGF), and epidermal growth factors(EGF) stimulate fibroblast proliferation and matrix secretion, andpromote leukocyte recruitment. The recruited leukocytes releaseadditional mediators such as fibroblast growth factors (FGF), vascularendothelial growth factors (VEGF), and other factors that reinforcefibroblast proliferation and differentiation, fight infection, andincrease vascular permeability and ingrowth. Although important in thewound healing process, inflammatory mediators such as TGF-β have beenimplicated in scar formation. Accordingly, it can be possible toattenuate scar formation by regulating the activity of mediatorsinvolved in the wound repair process. In an embodiment, astroglialcells, in their immature, activated state, can be used to reducesecondary cell death (necrosis) glial scar formation, promote axonregeneration, or promote blood vessel growth. See, e.g., U.S. Pat. No.4,900,553. For example, in an embodiment, a method of reducing glialscar formation includes inducing apoptosis in reactive astrocytes (e.g.,microglia, endothelial cells, fibroblasts, or the like), providing oneor more neural stem cells, nonreactive astrocytes or the like, andproviding a stimulus (an electrical, an electromagnetic, an ultrasonic,or a thermal stimulus, or the like) of a character and duration topromote growth of the one or more neural stem cells, or nonreactiveastrocytes.

At 3110, the method 3100 includes implanting or inserting a surgicalimplant comprising a photoactivatable steroid composition into abiological subject. In an embodiment, implanting or inserting thesurgical implant includes implanting or inserting a surgical implantcomprising a photoactivatable steroid composition including one or moregrowth promoting materials. At 3120, the method 3100 includesphotoactivating the photoactivatable steroid composition. At 3122,photoactivating the photoactivatable steroid composition includesactivating an actively controllable excitation component 910 so as todeliver a sterilizing energy stimulus of a character and for a timesufficient to photoactivate at least a portion of the photoactivatablesteroid composition. In an embodiment, photoactivating thephotoactivatable steroid composition includes controlling an activelycontrollable excitation component 910 so as to deliver a sterilizingenergy stimulus of a character and for a time sufficient to stimulatenon-scarring tissue formation. In an embodiment, the method 3100 canfurther include concurrently or sequentially delivering a firstelectrical stimulus and a second electrical stimulus, in vivo, to targettissue proximate the implanted or inserted surgical implant. In anembodiment, the first electrical stimulus or the second electricalstimulus is of a character and duration to inhibit growth of tissue of afirst type, and the other of the first electrical stimulus or the secondelectrical stimulus is of a character and duration to promote growth oftissue of a second type. In an embodiment, the method 3100 includesconcurrently or sequentially delivering a first electrical stimulus anda second electrical stimulus, in vivo, to target tissue proximate theimplanted or inserted surgical implant, such than the first electricalstimulus or the second electrical stimulus is of a character andduration to inhibit (e.g., minimize, reduce, prevent, or the like) ascar formation process, and the other of the first electrical stimulusor the second electrical stimulus is of a character and duration topromote growth of tissue. In an embodiment, the method 3100 can furtherinclude concurrently or sequentially delivering a spatially patternedelectrical stimulus including a first electrical stimulus and a secondelectrical stimulus, in vivo, to target tissue proximate the implantedor inserted surgical implant, the first electrical stimulus or thesecond electrical stimulus of a character and duration to inhibit scarformation in a first region proximate the implanted device and the otherof the first electrical stimulus or the second electrical stimulus of acharacter and duration to promote growth of tissue in a second regionproximate the implanted, the second region differing in at least one ofarea, volume, and location of the first region.

FIG. 32 shows an example of a method 3200 of treating scar formationpost surgery. At 3210, the method 3200 includes photoactivating aphotoactivatable steroid composition carried by an implanted surgicalimplant. At 3212, photoactivating the photoactivatable steroidcomposition includes activating an actively controllable excitationcomponent 910 to deliver a space-apart light energy patterned having asufficient strength or duration to photoactivate at least a portion ofthe photoactivatable steroid composition.

FIG. 33 shows an example of a method 3300 of forming an antimicrobialagent, in vivo. At 3310, the method 3300 includes providing aninterstitial fluid with a sufficient amount of electrical energy, via anindwelling implant including a plurality of energy emitters 302, toelicit the formation of superoxidized water. In an embodiment, theresulting superoxidized water can affect one or more healing or growthpromoting properties to tissue or a biological fluid. At 3312, providingthe interstitial fluids with the sufficient amount of electrical energyincludes applying a voltage of greater than about 650 millivolts (mV) toat least a portion of the interstitial fluid proximate the indwellingimplant. At 3314, providing the interstitial fluids with the sufficientamount of electrical energy includes applying a voltage of greater thanabout 800 millivolts (mV) to at least a portion of the interstitialfluid proximate the indwelling implant. Applying a sufficient voltage totissue infected with, for example, pathogenic bacteria, can lead to areduction of the pathogenic bacteria in at least a portion of theinfected tissue. At 3316, providing the interstitial fluids with thesufficient amount of electrical energy includes applying a voltage ofgreater than about 950 millivolts (mV) to at least a portion of theinterstitial fluid proximate the indwelling implant.

FIG. 34 shows an example of a method 3400 of forming an antimicrobialagent, in vivo. At 3410, the method 3400 includes delivering anenergy-activatable antimicrobial agent composition to a region (e.g., aregion within a fluid-flow passageway 106, a region proximate an inneror an outer surface of an implantable device 102, or the like) proximatean implanted or inserted surgical implant, the implanted or insertedsurgical implant including at least one antimicrobial agent reservoir,the antimicrobial agent reservoir configured to deliver anenergy-activatable antimicrobial agent composition to tissue proximatean outer surface of the surgical implant, and a plurality of electrodes,the plurality of electrodes operable to energize an energy-activatableantimicrobial agent composition in the presence of an applied potential.Among antimicrobial agent compositions, examples include, but are notlimited to, diluted solutions of NaCl, hypochlorous acid solutions(HAS), oxidative reduction potential aqueous compositions, STERILOX TX(PuriCore Inc.), STERILOX Solutions (PuriCore Inc.), MICROCYN (NofilCorp.), superoxidized aqueous compositions, superoxidized water,superoxide dismutase compositions, physiologically balanced ionizedacidic solutions, and the like. Further non-limiting examples ofantimicrobial agent compositions can be found in, for example, thefollowing documents (the contents of which are incorporated herein byreference): U.S. Pat. Nos. 7,276,255 (issued Oct. 2, 2007), 7,183,048(issued Feb. 27, 2007), 6,506,416 (issued Jan. 14, 2003), 6,426,066(issued Jul. 30, 2002), and 5,622,848 (Apr. 22, 1997); and U.S. PatentNos. 2007/0196357 (published Aug. 23, 2007), 2007/0173755 (publishedJul. 26, 2007), and 2005/0142157 (published Jun. 30, 2005).

At 3412, delivering an energy-activatable antimicrobial agentcomposition includes delivering an energy-activatable antimicrobialagent composition including at least one photoactive agent, or ametabolic precursor thereof. At 3414, delivering an energy-activatableantimicrobial agent composition includes delivering anenergy-activatable antimicrobial agent composition including at leastone X-ray absorber. At 3416, delivering an energy-activatableantimicrobial agent composition includes delivering anenergy-activatable antimicrobial agent composition including at leastone radiation absorber. At 3418, delivering an energy-activatableantimicrobial agent composition includes delivering anenergy-activatable antimicrobial agent composition including at leastone active agent that selectively targets bacteria.

At 3420, the method 3400 includes applying a sufficient potential to thedelivered energy-activatable antimicrobial agent composition to elicitthe formation of superoxide species. At 3422, applying the sufficientpotential to the delivered energy-activatable antimicrobial agentcomposition includes applying a sufficient potential to generate apotential of greater than about 650 millivolts (mV) in a regionproximate the outer surface of the surgical implant that includes aportion of the energy-activatable antimicrobial agent composition. At3424, applying the sufficient potential to the deliveredenergy-activatable antimicrobial agent composition includes applying asufficient potential to generate a potential of greater than about 800millivolts (mV) in a region proximate the outer surface of the surgicalimplant that includes a portion of the energy-activatable antimicrobialagent composition. At 3426, applying the sufficient potential to thedelivered energy-activatable antimicrobial agent composition includesapplying a sufficient potential to generate a potential of greater thanabout 950 millivolts (mV) in a region proximate the outer surface of thesurgical implant that includes a portion of the energy-activatableantimicrobial agent composition. In an embodiment, the antimicrobialagent compositions ranges in pH from about 5.0 to about 6.5. At 3428,applying the sufficient potential to the delivered energy-activatableantimicrobial agent composition includes applying a sufficient potentialto a NaCl composition proximate an implanted or inserted surgicalimplant, to electrolytically generate a hypochlorous acid solution(HAS), in vivo, in a region. In an embodiment, the pH of the generatedHAS ranges from about 5.5 to about 6.2.

FIG. 35 shows an example of a method 3500 of inhibiting a microbialcolonization in the cerebrospinal fluid of a biological subject. At3510, the method 3500 includes selectively energizing one or moreregions of at least one cerebrospinal fluid-flow passageway 106 of anindwelling implant 102 via one or more pulsed thermal stimuli emittingcomponents in response to an automatically detected optical densityparameter associated with a cerebrospinal fluid received within the atleast one cerebrospinal fluid-flow passageway 106. At 3512, selectivelyenergizing includes concurrently or sequentially delivering at least afirst pulsed thermal stimulus to a first region and a second pulsedthermal stimulus to a second region. At 3514, selectively energizingincludes concurrently or sequentially delivering a pulsed thermalstimulus to a first region and at least one of a pulsed electromagneticstimulus, a pulsed electrical s stimulus, or a pulsed ultrasonicstimulus to a second region. At 3520, the method 3500 can includedelivering an active agent composition to one or more regions of atleast one fluid-flow passageway 106 of an in vivo implantedcerebrospinal fluid management system 100 in response to anautomatically detected optical density parameter associated with acerebrospinal fluid received within the at least one fluid-flowpassageway 106.

FIG. 36 shows an example of a method 3600. At 3610, the method 3600includes providing a pulsed thermal sterilizing stimulus to an interiorof at least one cerebrospinal fluid-flow passageway 106 of an implanteddevice 102 in response to a change in a refractive index parameterindicative of a presence of an infectious agent within the at least onecerebrospinal fluid-flow passageway 106 of the implanted device 102. At3612, providing the pulsed thermal sterilizing stimulus includesproviding a spatially patterned pulsed thermal sterilizing stimulushaving at least a first region and a second region different from thefirst region. At 3614, providing the pulsed thermal sterilizing stimulusincludes providing a thermal pattern comprising at least a first regionand a second region, the second region having at least one of anintensity, an energy-emitting pattern, a peak emission, an ON-pulseduration, an OFF-pulse duration, or a pulse frequency different from thefirst region. At 3616, providing the pulsed thermal sterilizing stimulusincludes providing a voltage to a cerebrospinal fluid received withinthe interior of at least one fluid-flow passageway 106, the voltage ofsufficient strength or duration so as to cause a temperature elevationin region of a cerebrospinal fluid received within the at least onefluid-flow passageway 106 from about a 36° C. to a temperature rangingfrom greater than about 41° C. to less than about 63° C.

At 3620, the method 3600 can include providing a pulsed thermalsterilizing stimulus to a tissue proximate an outer surface of theimplanted device 102. At 3622, providing the pulsed thermal sterilizingstimulus includes independently delivering, in vivo, at least one of afirst pulsed thermal sterilizing stimulus to a cerebrospinal fluidreceived within the interior of at least one fluid-flow passageway 106and a second pulsed thermal sterilizing stimulus to a tissue proximatethe outer surface of the implanted device 102. At 3624, providing thepulsed thermal sterilizing stimulus includes independently delivering,in vivo, at least one of a first pulsed thermal sterilizing stimulus toa cerebrospinal fluid received within the interior of at least onefluid-flow passageway 106 and a second pulsed thermal sterilizingstimulus to a tissue proximate the outer surface of the implantedcerebrospinal fluid management device 102 in response to a real-timedetected change in an index of refraction parameter associated with thecerebrospinal fluid received within the interior of at least onefluid-flow passageway 106.

FIG. 37 shows an example of a method 3700. At 3710, the method 3700includes delivering one or more pulsed thermal stimuli to at least oneof an interior or an exterior of a cerebrospinal fluid-flow passageway106 of an indwelling implant apparatus 102 in response to an in vivodetected change in a refractive parameter indicative of a presence of aninfectious agent proximate the exterior or the interior of thecerebrospinal fluid-flow passageway 106. At 3712, delivering the one ormore pulsed thermal stimuli includes delivering one or more pulsedthermal stimuli to at least one of an interior or an exterior of acerebrospinal fluid-flow passageway 106 of an indwelling cerebrospinalfluid management implant 102.

FIG. 38 shows an example of a method 3800. At 3810, the method 3800includes concurrently or sequentially delivering two or more energystimuli to an interior surface 110 and an exterior surface 108 of a bodystructure 104 of an indwelling apparatus in response to a detectedparameter associated with one or more of a cerebrospinal fluid receivedwithin the interior of the body structure 104, a detected parameterassociated with a tissue proximate the exterior surface 108, or aphysiological characteristic associated with a biological subject.

At least a portion of the devices and/or processes described herein canbe integrated into a data processing system. A data processing systemgenerally includes one or more of a system unit housing, a video displaydevice, memory such as volatile or non-volatile memory, processors suchas microprocessors or digital signal processors, computational entitiessuch as operating systems, drivers, graphical user interfaces, andapplications programs, one or more interaction devices (e.g., a touchpad, a touch screen, an antenna, etc.), and/or control systems includingfeedback loops and control motors (e.g., feedback for detecting positionand/or velocity, control motors for moving and/or adjusting componentsand/or quantities). A data processing system can be implementedutilizing suitable commercially available components, such as thosetypically found in data computing/communication and/or networkcomputing/communication systems.

The herein described subject matter sometimes illustrates differentcomponents contained within, or connected with, different othercomponents. It is to be understood that such depicted architectures aremerely examples, and that in fact, many other architectures can beimplemented that achieve the same functionality. In a conceptual sense,any arrangement of components to achieve the same functionality iseffectively “associated” such that the desired functionality isachieved. Hence, any two components herein combined to achieve aparticular functionality can be seen as “associated with” each othersuch that the desired functionality is achieved, irrespective ofarchitectures or intermedial components. Likewise, any two components soassociated can also be viewed as being “operably connected”, or“operably coupled,” to each other to achieve the desired functionality,and any two components capable of being so associated can also be viewedas being “operably coupleable,” to each other to achieve the desiredfunctionality. Specific examples of operably coupleable include, but arenot limited to, physically mateable and/or physically interactingcomponents, and/or wirelessly interactable, and/or wirelesslyinteracting components, and/or logically interacting, and/or logicallyinteractable components.

In an embodiment, one or more components may be referred to herein as“configured to,” “configurable to,” “operable/operative to,”“adapted/adaptable,” “able to,” “conformable/conformed to,” etc. Suchterms (e.g., “configured to”) can generally encompass active-statecomponents and/or inactive-state components and/or standby-statecomponents, unless context requires otherwise.

The foregoing detailed description has set forth various embodiments ofthe devices and/or processes via the use of block diagrams, flowcharts,and/or examples. Insofar as such block diagrams, flowcharts, and/orexamples contain one or more functions and/or operations, it will beunderstood by the reader that each function and/or operation within suchblock diagrams, flowcharts, or examples can be implemented, individuallyand/or collectively, by a wide range of hardware, software, firmware, orvirtually any combination thereof. Further, the use of “Start,” “End” or“Stop” blocks in the block diagrams is not intended to indicate alimitation on the beginning or end of any functions in the diagram. Suchflowcharts or diagrams may be incorporated into other flowcharts ordiagrams where additional functions are performed before or after thefunctions shown in the diagrams of this application. In an embodiment,several portions of the subject matter described herein is implementedvia Application Specific Integrated Circuits (ASICs), Field ProgrammableGate Arrays (FPGAs), digital signal processors (DSPs), or otherintegrated formats. However, some aspects of the embodiments disclosedherein, in whole or in part, can be equivalently implemented inintegrated circuits, as one or more computer programs running on one ormore computers (e.g., as one or more programs running on one or morecomputer systems), as one or more programs running on one or moreprocessors (e.g., as one or more programs running on one or moremicroprocessors), as firmware, or as virtually any combination thereof,and that designing the circuitry and/or writing the code for thesoftware and or firmware would be well within the skill of one of skillin the art in light of this disclosure. In addition, the mechanisms ofthe subject matter described herein are capable of being distributed asa program product in a variety of forms, and that an illustrativeembodiment of the subject matter described herein applies regardless ofthe particular type of signal-bearing medium used to actually carry outthe distribution. Non-limiting examples of a signal-bearing mediuminclude the following: a recordable type medium such as a floppy disk, ahard disk drive, a Compact Disc (CD), a Digital Video Disk (DVD), adigital tape, a computer memory, etc.; and a transmission type mediumsuch as a digital and/or an analog communication medium (e.g., a fiberoptic cable, a waveguide, a wired communications link, a wirelesscommunication link (e.g., transmitter, receiver, transmission logic,reception logic, etc.), etc.).

While particular aspects of the present subject matter described hereinhave been shown and described, it will be apparent to the reader that,based upon the teachings herein, changes and modifications can be madewithout departing from the subject matter described herein and itsbroader aspects and, therefore, the appended claims are to encompasswithin their scope all such changes and modifications as are within thetrue spirit and scope of the subject matter described herein. Ingeneral, terms used herein, and especially in the appended claims (e.g.,bodies of the appended claims) are generally intended as “open” terms(e.g., the term “including” should be interpreted as “including but notlimited to,” the term “having” should be interpreted as “having atleast,” the term “includes” should be interpreted as “includes but isnot limited to,” etc.). Further, if a specific number of an introducedclaim recitation is intended, such an intent will be explicitly recitedin the claim, and in the absence of such recitation no such intent ispresent. For example, as an aid to understanding, the following appendedclaims may contain usage of the introductory phrases “at least one” and“one or more” to introduce claim recitations. However, the use of suchphrases should not be construed to imply that the introduction of aclaim recitation by the indefinite articles “a” or “an” limits anyparticular claim containing such introduced claim recitation to claimscontaining only one such recitation, even when the same claim includesthe introductory phrases “one or more” or “at least one” and indefinitearticles such as “a” or “an” (e.g., “a” and/or “an” should typically beinterpreted to mean “at least one” or “one or more”); the same holdstrue for the use of definite articles used to introduce claimrecitations. In addition, even if a specific number of an introducedclaim recitation is explicitly recited, such recitation should typicallybe interpreted to mean at least the recited number (e.g., the barerecitation of “two recitations,” without other modifiers, typicallymeans at least two recitations, or two or more recitations).Furthermore, in those instances where a convention analogous to “atleast one of A, B, and C, etc.” is used, in general such a constructionis intended in the sense of the convention (e.g., “a system having atleast one of A, B, and C” would include but not be limited to systemsthat have A alone, B alone, C alone, A and B together, A and C together,B and C together, and/or A, B, and C together, etc.). In those instanceswhere a convention analogous to “at least one of A, B, or C, etc.” isused, in general such a construction is intended in the sense of theconvention (e.g., “a system having at least one of A, B, or C” wouldinclude but not be limited to systems that have A alone, B alone, Calone, A and B together, A and C together, B and C together, and/or A,B, and C together, etc.). Typically a disjunctive word and/or phrasepresenting two or more alternative terms, whether in the description,claims, or drawings, should be understood to contemplate thepossibilities of including one of the terms, either of the terms, orboth terms unless context dictates otherwise. For example, the phrase “Aor B” will be typically understood to include the possibilities of “A”or “B” or “A and B.”

With respect to the appended claims, the operations recited thereingenerally may be performed in any order. Also, although variousoperational flows are presented in a sequence(s), it should beunderstood that the various operations may be performed in orders otherthan those that are illustrated, or may be performed concurrently.Examples of such alternate orderings includes overlapping, interleaved,interrupted, reordered, incremental, preparatory, supplemental,simultaneous, reverse, or other variant orderings, unless contextdictates otherwise. Furthermore, terms like “responsive to,” “relatedto,” or other past-tense adjectives are generally not intended toexclude such variants, unless context dictates otherwise.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments are contemplated. The various aspects andembodiments disclosed herein are for purposes of illustration and arenot intended to be limiting, with the true scope and spirit beingindicated by the following claims.

1.-699. (canceled)
 700. An implantable fluid management device,comprising: a cerebrospinal fluid catheter assembly defining one or morefluid-flow passageways configured to receive a biological fluid of asubject; a first actively controllable excitation component configuredto deliver, in vivo, a first sterilizing energy stimulus to a biologicalfluid received within at least one of the one or more fluid-flowpassageways; a second actively controllable excitation componentconfigured to deliver, in vivo, a second sterilizing energy stimulus toa tissue proximate an outer surface of the implantable fluid managementdevice; and a control means operably coupled to at least one of thefirst actively controllable excitation component and the second activelycontrollable excitation component.
 701. The implantable fluid managementdevice of claim 700, wherein the implantable fluid management device isconfigured to concurrently or sequentially deliver the first sterilizingenergy stimulus to a biological fluid received within at least one ofthe one or more fluid-flow passageways and the second sterilizing energystimulus to a tissue proximate an outer surface of the implantable fluidmanagement device.
 702. The implantable fluid management device of claim700, wherein the first sterilizing energy stimulus or the secondsterilizing energy stimulus comprises an electromagnetic stimulus, anelectrical stimulus, an ultrasonic stimulus, or a thermal stimulus. 703.The implantable fluid management device of claim 700, wherein the firststerilizing energy stimulus comprises one of an electrical sterilizingenergy stimulus, an electromagnetic sterilizing energy stimulus, anultrasonic sterilizing energy stimulus, or a thermal sterilizing energystimulus, and the second sterilizing energy stimulus comprises adifferent one of an electrical sterilizing energy stimulus, anelectromagnetic sterilizing energy stimulus, an ultrasonic sterilizingenergy stimulus, or a thermal sterilizing energy stimulus.
 704. Theimplantable fluid management device of claim 700, wherein theimplantable fluid management device is configured to concurrently orsequentially deliver at least a first energy stimulus and a secondenergy stimulus, the second energy stimulus different from the firstenergy stimulus; wherein the first energy stimulus comprises one of anelectromagnetic energy stimulus, an electrical energy stimulus, anultrasonic energy stimulus, or a thermal energy stimulus, and the secondenergy stimulus comprises a different one of an electromagnetic energystimulus, an electrical energy stimulus, an ultrasonic energy stimulus,or a thermal energy stimulus.
 705. The implantable fluid managementdevice of claim 700, wherein the implantable fluid management device isconfigured to provide an illumination pattern to a biological fluidreceived within at least one of the one or more fluid-flow passageways,the illumination pattern comprising at least a first region and a secondregion, the second region having at least one of an illuminationintensity, an energy-emitting pattern, a peak emission wavelength, anON-pulse duration, an OFF-pulse duration, and a pulse frequencydifferent from the first region.
 706. The implantable fluid managementdevice of claim 700, wherein the implantable fluid management device isconfigured to provide an illumination pattern to a tissue proximate anouter surface of the implantable fluid management device, theillumination pattern comprising at least a first region and a secondregion, the second region having at least one of an illuminationintensity, an energy-emitting pattern, a peak emission wavelength, anON-pulse duration, an OFF-pulse duration, and a pulse frequencydifferent from the first region.
 707. The implantable fluid managementdevice of claim 700, wherein the implantable fluid management device isconfigured to concurrently or sequentially emit at least one of thefirst sterilizing energy stimulus and the second sterilizing energystimulus of a character and for a time sufficient to inactivate aninfectious agent proximate an outer or inner portion of the implantabledevice.
 708. An implantable fluid management device, comprising: acerebrospinal fluid catheter assembly defining one or more fluid-flowpassageways configured to receive a biological fluid of a subject; anactively controllable excitation component configured to independentlydeliver, in vivo, at least one of a first sterilizing energy stimulus toa biological fluid received within at least one of the one or morefluid-flow passageways and a second sterilizing energy stimulus to atissue proximate an outer surface of the implantable fluid managementdevice; and a control means operably coupled to the activelycontrollable excitation component.
 709. The implantable fluid managementdevice of claim 708, wherein the actively controllable excitationcomponent is configured to concurrently or sequentially deliver thefirst sterilizing energy stimulus to a biological fluid received withinat least one of the one or more fluid-flow passageways and the secondsterilizing energy stimulus to a tissue proximate an outer surface ofthe implantable fluid management device.
 710. The implantable fluidmanagement device of claim 708, wherein the first sterilizing energystimulus or the second sterilizing energy stimulus comprises anelectromagnetic stimulus, an electrical stimulus, an ultrasonicstimulus, or a thermal stimulus.
 711. The implantable fluid managementdevice of claim 708, wherein the first sterilizing energy stimuluscomprises one of an electrical sterilizing energy stimulus, anelectromagnetic sterilizing energy stimulus, an ultrasonic sterilizingenergy stimulus, or a thermal sterilizing energy stimulus, and thesecond sterilizing energy stimulus comprises a different one of anelectrical sterilizing energy stimulus, an electromagnetic sterilizingenergy stimulus, an ultrasonic sterilizing energy stimulus, or a thermalsterilizing energy stimulus.
 712. The implantable fluid managementdevice of claim 708, wherein the actively controllable excitationcomponent is configured to concurrently or sequentially deliver at leasta first energy stimulus and a second energy stimulus, the second energystimulus different from the first energy stimulus; wherein the firstenergy stimulus comprises one of an electromagnetic energy stimulus, anelectrical energy stimulus, an ultrasonic energy stimulus, or a thermalenergy stimulus, and the second energy stimulus comprises a differentone of an electromagnetic energy stimulus, an electrical energystimulus, an ultrasonic energy stimulus, or a thermal energy stimulus.713. The implantable fluid management device of claim 708, wherein theactively controllable excitation component is configured to provide anillumination pattern to a biological fluid received within at least oneof the one or more fluid-flow passageways, the illumination patterncomprising at least a first region and a second region, the secondregion having at least one of an illumination intensity, anenergy-emitting pattern, a peak emission wavelength, an ON-pulseduration, an OFF-pulse duration, and a pulse frequency different fromthe first region.
 714. The implantable fluid management device of claim708, wherein the actively controllable excitation component isconfigured to provide an illumination pattern to a tissue proximate anouter surface of the implantable fluid management device, theillumination pattern comprising at least a first region and a secondregion, the second region having at least one of an illuminationintensity, an energy-emitting pattern, a peak emission wavelength, anON-pulse duration, an OFF-pulse duration, and a pulse frequencydifferent from the first region.
 715. The implantable fluid managementdevice of claim 708, wherein the actively controllable excitationcomponent is configured to concurrently or sequentially emit at leastone of the first sterilizing energy stimulus and the second sterilizingenergy stimulus of a character and for a time sufficient to inactivatean infectious agent present in the biological fluid received within atleast one of the one or more fluid-flow passageways and the tissueproximate an outer surface of the implantable fluid management device.716. The implantable fluid management device of claim 708, furthercomprising: a cryptographic logic component.
 717. The implantable fluidmanagement device of claim 716, wherein the cryptographic logiccomponent is configured to implement at least one cryptographic processor cryptographic logic.
 718. The implantable fluid management device ofclaim 716, wherein the cryptographic logic component is configured toimplement one or more processes associated with at least one of acryptographic protocol, a decryption protocol, and an encryptionprotocol.
 719. The implantable fluid management device of claim 716,wherein the cryptographic logic component is configured to implement oneor more processes associated with at least one of a regulatorycompliance protocol, a regulatory use protocol, an authenticationprotocol, an authorization protocol, a delivery protocol, and anactivation protocol.
 720. The implantable fluid management device ofclaim 716, wherein the cryptographic logic component comprises one ormore crypto-algorithms, signal-bearing media, crypto controllers, orcryptographic modules.
 721. The implantable fluid management device ofclaim 716, wherein the cryptographic logic component is configured togenerate information associated with at least one of an authenticationprotocol, an authorization protocol, a delivery protocol, an activationprotocol, an encryption protocol, and a decryption protocol.
 722. Theimplantable fluid management device of claim 716, wherein thecryptographic logic component is configured to generate informationassociated at least one of an authorization instruction, anauthentication instruction, a prescription dosing instruction, asterilizing energy stimulus administration instruction, and a prescribedregimen instruction. 723.-754. (canceled)